Porous inorganic/organic hybrid monolith materials for chromatographic separations and process for their preparation

ABSTRACT

Novel materials for chromatographic separations, processes for their preparation, and separation devices containing the chromatographic materials. In particular, the novel materials are porous inorganic/organic hybrid monolith materials, which desirably may be surface modified, and which offer more efficient chromatographic separations than that known in the art.

RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.11/644,279, filed Dec. 21, 2006, now U.S. Pat. No. 8,404,346, issued onMar. 26, 2013, which patent is a divisional of U.S. application Ser. No.10/216,674, filed Aug. 8, 2002, now U.S. Pat. No. 7,250,214, whichclaims priority to U.S. Provisional Patent Application No. 60/311,445,filed Aug. 9, 2001, the contents of each of which are hereby expresslyincorporated herein by reference in its their entireties.

BACKGROUND OF THE INVENTION

Packing materials for liquid chromatography (LC) are generallyclassified into two types: organic materials, e.g., polydivinylbenzene,and inorganic materials typified by silica. Many organic materials arechemically stable against strongly alkaline and strongly acidic mobilephases, allowing flexibility in the choice of mobile phase pH. However,organic chromatographic materials generally result in columns with lowefficiency, leading to inadequate separation performance, particularlywith low molecular-weight analytes. Furthermore, many organicchromatographic materials shrink and swell when the composition of themobile phase is changed. In addition, most organic chromatographicmaterials do not have the mechanical strength of typical chromatographicsilicas.

Due in large part to these limitations, silica is the material mostwidely used in High Performance Liquid Chromatography (HPLC). The mostcommon applications employ silica that has been surface-derivatized withan organic group such as octadecyl (C₁₈), octyl (C₈), phenyl, amino,cyano, etc. As stationary phases for HPLC, these packing materialsresult in columns that have high efficiency and do not show evidence ofshrinking or swelling.

Silica is characterized by the presence of silanol groups on itssurface. During a typical derivatization process such as reaction withoctadecyldimethylchlorosilane, at least 50% of the surface silanolgroups remains unreacted. These residual silanol groups interact withbasic and acidic analytes via ion exchange, hydrogen bonding anddipole/dipole mechanisms. The residual silanol groups create problemsincluding increased retention, excessive peak tailing and irreversibleadsorption of some analytes. Another drawback with silica-based columnsis their limited hydrolytic stability. First, the incompletederivatization of the silica leaves patches of bare silica surface whichcan be readily dissolved under alkaline conditions, generally pH>8.0,leading to the subsequent collapse of the chromatographic bed. Second,the bonded phase can be stripped off the surface under acidicconditions, generally pH<2.0, and eluted off the column by the mobilephase, causing loss of analyte retention, and an increase in theconcentration of surface silanol groups.

To overcome the problems of residual silanol group activity andhydrolytic instability of silica-based stationary phases, many methodshave been tried including use of ultrapure silica, carbonized silica,coating of the silica surface with polymeric materials, endcapping freesilanol groups with a short-chain reagent such as trimethylsilane, andthe addition of suppressors such as amines to the eluant. Theseapproaches have not proven to be completely satisfactory in practice.

One approach is disclosed in U.S. Pat. No. 4,017,528. A process forpreparing a hybrid silica is described wherein an alkyl functionality iscoupled into both the skeleton structure and the surface of the silica.According to the '528 patent, the hybrid silica can be prepared by twomethods. In the first method, a mixture of tetraethoxysilane (TEOS) andan organotriethoxysilane, e.g., alkyltriethoxysilane, is co-hydrolyzedin the presence of an acid catalyst to form a liquid material containingpolyorganoethoxysiloxane (POS) oligomers, e.g., polyalkylethoxysiloxaneoligomers. Then, the POS is suspended in an aqueous medium and gelledinto porous hybrid particles in the presence of a base catalyst. In thesecond method, the material is prepared by a similar procedure exceptthat the suspension droplet is a mixture of organotriethoxysilane, e.g.,alkyltriethoxysilane, and polyethoxysiloxane (PES) oligomers; the latteris prepared by partial hydrolysis of TEOS.

There are several problems associated with the '528 hybrid material.First, these hybrid materials contain numerous micropores, i.e., poreshaving a diameter below about 34 Å. It is known that such microporesinhibit solute mass transfer, resulting in poor peak shape and bandbroadening.

Second, the pore structure of the '528 hybrid material is formed becauseof the presence of ethanol (a side product of the gelation process)within the suspension oil droplets. The pore volume is controlled by themolecular weight of the POS or PES. The lower the molecular weight ofthe POS or PES, the more ethanol is generated during the gelationreaction, and subsequently a larger pore volume is produced. However,part of the ethanol generated during the gelation is able to diffuseinto the aqueous phase by partition. If the amount of the ethanolgenerated within the suspension droplets is too great, the partition ofthe ethanol will cause the structure of the droplets to collapse,forming irregularly-shaped particles as opposed to spherical particles.Therefore, the strategy to control the pore volume of the hybridmaterial described in the '528 patent has certain limitations,particularly for preparing highly spherical hybrid materials with a porevolume greater than about 0.8 cm³/g. It is well known in the art thatirregularly-shaped materials are generally more difficult to pack thanspherical materials. It is also known that columns packed withirregularly-shaped materials generally exhibit poorer packed bedstability than spherical materials of the same size.

Third, the '528 hybrid materials are characterized by an inhomogeneousparticle morphology, which contributes to undesirable chromatographicproperties, including poor mass transfer properties for solutemolecules. This is a consequence of the gelation mechanism, where thebase catalyst reacts rapidly near the surface of the POS droplet,forming a “skinned” layer having very small pores. Further gelation inthe interior of the droplet is then limited by the diffusion of catalystthrough this outer layer towards the droplet center, leading toparticles having skeletal morphologies and hence pore geometries, e.g.,“shell shaped”, which can vary as a function of location between theparticle center and outer layer.

A further problem associated with silica particles and polymer particlesis packed bed stability. Chromatography columns packed with sphericalparticles can be considered to be random close packed lattices in whichthe interstices between the particles form a continuous network from thecolumn inlet to the column outlet. This network forms the interstitialvolume of the packed bed which acts as a conduit for fluid to flowthrough the packed column. In order to achieve maximum packed bedstability, the particles must be tightly packed, and hence, theinterstitial volume is limited in the column. As a result, such tightlypacked columns afford high column backpressures which are not desirable.Moreover, bed stability problems for these chromatography columns arestill typically observed, because of particle rearrangements.

In an attempt to overcome the problem of packed bed stability, severalgroups have reported studies on stabilizing the packed bed by sinteringor interconnecting inorganic, e.g., silica based particles. In thesintering process, particles are joined to one another by grainboundaries. In one approach, previously prepared octadecylsilicaparticles are immobilized in a sol-gel matrix or a polymer matrixprepared in situ in a chromatography column. In another approach,agglomeration of the silica based C-18 particles at high temperature hasbeen reported (M. T. Dulay, R. P. Kulkarni, R. N. Zare, Anal. Chem., 70(1998) 5103; Xin, B.; Lee, M. L. Electrophoresis 1999, 20, 67; Q. Tang,B. Xin, M. L. Lee, J. Chromatogr. A, 837 (1999) 35.; Q. Tang, N. Wu, M.L. Lee, J. Microcolumn Separations, 12 (2000) 6.; R. Asiaie, X. Huang,D. Farnan, Cs. Horvath, J. Chromatogr. A, 806 (1998) 251). In addition,interconnection of silica particles surface modified by Al chelatecompounds (S. Ueno, K. Muraoka, H. Yoshimatsu, A. Osaka, Y Miura,Journal-Ceramic Society Japan, 109 (2001) 210.) and microwave sinteringof silica particles (A. Goldstein, R. Ruginets, Y. Geffen, J. of Mat.Sci. Letters, 16 (1997) 310) have been reported. The interstitialporosity of the above particle-sintered or interconnected columns, andhence the permeability of the columns obtained by this approach is lessthan or similar to those of the conventional packed columns Therefore,the backpressures of the column are the same or higher than those of theconventional packed columns, and result in an inability to achieve highefficiency chromatographic separations at low backpressures and highflow rates.

In an attempt to overcome the combined problems of packed bed stabilityand high efficiency separations at low backpressures and high flowrates, several groups have reported the use of monolith materials inchromatographic separations. Monolith materials are characterized by acontinuous, interconnected pore structure of large macropores, the sizeof which can be changed independent of the skeleton size without causingbed instability. The large macropores allow liquid to flow directlythrough with very little resistance resulting in very low backpressures,even at high flow rates.

However there are several critical drawbacks associated with existingmonolith materials. Columns made using organic monolith materials, e.g.,polydivinylbenzene, generally have low efficiency, particularly for lowmolecular weight analytes. Although organic monoliths are chemicallystable against strongly alkaline and strongly acidic mobile phases, theyare limited in the composition of organic solvent in the mobile phasedue to shrinking or swelling of the organic polymer, which cannegatively affect the performance of these monolithic columns. Forexample, as a result of monolith shrinking, the monolith can losecontact with the wall and thus allow the eluent to by-pass the bed,whereupon chromatographic resolution is dramatically decreased. Despitethe fact that organic polymeric monoliths of many different compositionsand processes have been explored, no solutions have been found to theseproblems.

In addition, chromatographic columns have also been made from inorganicmonolith materials, e.g., silica. Inorganic silica monoliths do not showevidence of shrinking and swelling, and exhibit higher efficiencies thantheir organic polymeric counterparts in chromatographic separations.However, silica monoliths suffer from the same major disadvantagesdescribed previously for silica particles: residual silanol groups aftersurface derivatization create problems that include increased retention,excessive tailing, irreversible adsorption of some analytes, and thedissolution of silica at alkaline pH values. In fact, as the variationof the pH is one of the most powerful tools in the manipulation ofchromatographic selectivity, there is a need to expand the use ofchromatographic separations into the alkaline pH range for monolithmaterials, without sacrificing analyte efficiency, retention andcapacity.

Hybrid silica monoliths offer a potential solution to overcome theproblems of residual silanol group activity and hydrolytic instabilityof silica-based monoliths, wherein an alkyl functionality is coupledinto both the skeleton structure and the surface of the silica. Severalapproaches are disclosed in U.S. Pat. No. 6,207,098 and Japanese patentapplication 2,893,104. However, the materials produced by the processesdisclosed in these patents require a calcination step to form the porousgel. At temperatures above 400° C., many organic groups on the surfacecan be destroyed, leaving the surface unprotected. Furthermore, silanolgroups can be irreversibly condensed above 400° C., leaving behind moreacidic silanols. As a result, some analytes, particularly basicanalytes, can suffer from increased retention, excessive tailing andirreversible adsorption. In addition, the hybrid monoliths produced bythis process contain numerous micropores, i.e., pores having a diameterbelow 34 Å, which are known to inhibit solute mass transfer, resultingin poor peak shape and band broadening.

In an alternative approach, U.S. Pat. No. 5,869,152 discloses a hybridsilica wherein at least a portion of silicon is bonded to an alkylmoiety. However, the materials produced by this process are essentiallyunimodal in their pore size and lack mesopores to create a surface areasufficient for long analyte retention and high analyte loading capacityin a reversed-phase (RP) HPLC mode.

SUMMARY OF THE INVENTION

The present invention relates to novel porous inorganic/organic hybridmaterials and their use in chromatographic separations, processes fortheir preparation, and separations devices containing thechromatographic material. Thus, one aspect of the invention is a porousinorganic/organic hybrid material, comprising achromatographically-enhancing pore geometry.

Another aspect of the invention is directed to a porousinorganic/organic hybrid material, wherein pores of a diameter of lessthan about 34 Å contribute less than about 110 m²/g to less than about50 m²/g to the specific surface area of the material.

Yet another aspect of the invention is a porous inorganic/organic hybridmonolith material, comprising a chromatographically-enhancing poregeometry.

Still another aspect of the invention is a porous inorganic/organichybrid monolith material, wherein pores of a diameter of less than about34 Å contribute less than about 110 m²/g to less than about 50 m²/g tothe specific surface area of the material.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material, comprising coalesced porous inorganic/organic hybridparticles having a chromatographically-enhancing pore geometry.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material, comprising coalesced porous inorganic/organic hybridparticles that have a chromatographically-enhancing pore geometry,wherein said particles have been surface modified by a surface modifierselected from the group consisting of an organic group surface modifier,a silanol group surface modifier, a polymeric coating surface modifier,and combinations thereof.

Another aspect of the present invention is a method of preparation of aporous inorganic/organic hybrid monolith material, comprising porousinorganic/organic hybrid particles having achromatographically-enhancing pore geometry, comprising the steps of

-   -   a) forming porous inorganic/organic hybrid particles,    -   b) modifying the pore structure of the porous hybrid particles,        and    -   c) coalescing the porous hybrid particles to form a monolith        material.

An additional aspect of the invention is a method of preparation of aporous inorganic/organic hybrid monolith material, comprising porousinorganic/organic hybrid particles that have achromatographically-enhancing pore geometry, comprising the steps of

-   -   a) forming porous inorganic/organic hybrid particles,    -   b) modifying the pore structure of said porous hybrid particles,    -   c) surface modifying said porous hybrid particles, and    -   d) coalescing said porous hybrid particles to form a monolith        material,        wherein said particles have been surface modified by a surface        modifier selected from the group consisting of an organic group        surface modifier, a silanol group surface modifier, a polymeric        coating surface modifier, and combinations thereof.

In another aspect, the invention is separations device comprising aporous inorganic/organic hybrid monolith material having achromatographically-enhancing pore geometry.

In yet another aspect, the invention is a separations device comprisinga porous inorganic/organic hybrid monolith material, wherein saidmonolith material has a chromatographically-enhancing pore geometry andis comprised of coalesced porous inorganic/organic hybrid particles, andwherein said particles have been surface modified by a surface modifierselected from the group consisting of an organic group surface modifier,a silanol group surface modifier, a polymeric coating surface modifier,and combinations thereof.

Another aspect of the invention is a chromatographic column havingimproved lifetime, comprising

-   -   a) a column having a cylindrical interior for accepting a        monolith material of porous inorganic/organic hybrid material,        and    -   b) a chromatographic bed comprising a porous inorganic/organic        hybrid monolith material having a chromatographically-enhancing        pore geometry of the formula SiO₂/(R² _(p)R⁴ _(q)SiO_(t))_(n) or        SiO₂/[R² _(r)SiO_(t))_(m)]_(n) wherein R² and R⁴ are        independently C₁-C₁₈ aliphatic, styryl, vinyl, propanol, or        aromatic moieties, R⁶ is a substituted or unsubstituted C₁-C₁₈        alkylene, alkenylene, alkynylene or arylene moiety bridging two        or more silicon atoms, p and q are 0, 1 or 2, provided that        p+q=1 or 2, and that when p+q=1, t=1.5, and when p+q=2, t=1; r        is 0 or 1, provided that when r=0, t=1.5, and when r=1, t=1; m        is an integer greater than or equal to 2, and n is a number from        0.03 to 1.

Yet another aspect of the invention is a chromatographic column havingimproved lifetime, comprising

-   -   a) a column having a cylindrical interior for accepting a        monolith material of porous inorganic/organic hybrid material,        and    -   b) a chromatographic bed comprising a porous inorganic/organic        hybrid monolith material having a chromatographically-enhancing        pore geometry, wherein said monolith material has been surface        modified by a surface modifier selected from the group        consisting of an organic group surface modifier, a silanol group        surface modifier, a polymeric coating surface modifier, and        combinations thereof.

In addition, one aspect of the invention is a method of preparation of aporous inorganic/organic hybrid monolith material, comprising coalescedporous particles of hybrid silica having a chromatography-enhancing poregeometry, comprising the steps of

-   -   a) prepolymerizing a mixture of one or more organoalkoxysilanes        and a tetraalkoxysilane in the presence of an acid catalyst to        produce a polyorganoalkoxysiloxane;    -   b) preparing an aqueous suspension of the        polyorganoalkoxysiloxane, the suspension further comprising a        surfactant or combination of surfactants, and gelling in the        presence of a base catalyst so as to produce porous hybrid        particles;    -   c) modifying the pore structure of the porous hybrid particles        by hydrothermal treatment; and    -   d) coalescing the porous hybrid particles to form a monolith        material thereby preparing a porous inorganic/organic hybrid        monolith material.

In another aspect, the present invention is a porous inorganic/organichybrid monolith material comprising coalesced porous hybrid particles ofhybrid silica having a chromatographically-enhancing pore geometry,produced by the process of

-   -   a) prepolymerizing a mixture of one or more organoalkoxysilanes        and a tetraalkoxysilane in the presence of an acid catalyst to        produce a polyorganoalkoxysiloxane;    -   b) preparing an aqueous suspension of the        polyorganoalkoxysiloxane, the suspension further comprising a        surfactant or a combination of surfactants, and gelling in the        presence of a base catalyst so as to produce porous hybrid        particles;    -   c) modifying the pore structure of the porous hybrid particles        by hydrothermal treatment; and    -   d) coalescing the porous hybrid particles to form a monolith        material.

Another aspect of the invention is porous inorganic/organic hybridmonolith material having a chromatographically-enhancing pore geometry,wherein said material contains a plurality of macropores sufficient toresult in reduced backpressure at chromatographically-useful flow rates.

Yet another aspect of the invention is a porous inorganic/organic hybridmonolith material, having a chromatographically-enhancing pore geometry,wherein said monolith material has been surface modified by a surfacemodifier selected from the group consisting of an organic group surfacemodifier, a silanol group surface modifier, a polymeric coating surfacemodifier, and combinations thereof.

An additional aspect of the invention is a method of preparation of aporous inorganic/organic hybrid monolith material having achromatographically-enhancing pore geometry, comprising the steps of

-   -   a) forming a porous inorganic/organic monolith material and    -   b) modifying the pore structure of said porous monolith        material.

In yet another aspect, the present invention is a method of preparationof a porous inorganic/organic hybrid monolith material having achromatographically-enhancing pore geometry, comprising the steps of

-   -   a) forming a porous inorganic/organic monolith material,    -   b) modifying the pore structure of said porous monolith        material, and    -   c) modifying the surface of said porous monolith material,        wherein said monolith material has been surface modified by a        surface modifier selected from the group consisting of an        organic group surface modifier, a silanol group surface        modifier, a polymeric coating surface modifier, and combinations        thereof.

Another aspect of the invention is separations device comprising aporous inorganic/organic hybrid monolith material having achromatographically-enhancing pore geometry, wherein said monolithmaterial has been surface modified by a surface modifier selected fromthe group consisting of an organic group surface modifier, a silanolgroup surface modifier, a polymeric coating surface modifier, andcombinations thereof.

In addition, one aspect of the invention is a method of preparation of aporous inorganic/organic hybrid monolith material having achromatographically-enhancing pore geometry comprising

-   -   a) preparing an aqueous solution of a mixture of one or more        organoalkoxysilanes and a tetraalkoxysilane in the presence of        an acid catalyst, and a surfactant or combination of surfactants        to produce a polyorganoalkoxysiloxane;    -   b) incubating said solution, resulting in a three-dimensional        gel having a continuous, interconnected pore structure,    -   c) aging the gel at a controlled pH and temperature to yield a        solid monolith material,    -   d) rinsing the monolith material with an aqueous basic solution        at an elevated temperature,    -   e) modifying the pore structure of said monolith material by        hydrothermal treatment,    -   f) rinsing the monolith material with water followed by a        solvent exchange, and    -   g) drying the monolith material at room temperature drying and        at an elevated temperature under vacuum        thereby preparing a porous inorganic/organic hybrid monolith        material.

In yet another aspect, the present invention is porous inorganic/organichybrid monolith material having a chromatographically-enhancing poregeometry, produced by the process of

-   -   a) preparing an aqueous solution of a mixture of one or more        organotrialkoxysilanes and a tetraalkoxysilane in the presence        of an acid catalyst, and a surfactant or combination of        surfactants to produce a polyorganoalkoxysiloxane;    -   b) incubating said solution, resulting in a three-dimensional        gel having a continuous, interconnected pore structure,    -   c) aging the gel at a controlled pH and temperature to yield a        solid monolith material, and    -   d) rinsing the monolith material with an aqueous basic solution        at an elevated temperature    -   e) modifying the pore structure of said monolith material by        hydrothermal treatment,    -   f) rinsing the monolith material with water followed by a        solvent exchange, and    -   g) drying the monolith material at room temperature drying and        at an elevated temperature under vacuum.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material, comprising coalesced porous inorganic/organic hybridparticles having a chromatographically-enhancing pore geometry and aformula SiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) wherein said hybrid particleshave been surface modified with octadecyltrichlorosilane and wherein anyfree silanol groups remaining from said surface modification areendcapped with chlorotrimethylsilane.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material comprising coalesced porous hybrid particles of hybridsilica having a chromatographically-enhancing pore geometry and aformula SiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) produced by the process of

-   -   a) prepolymerizing a 0.25/1.0 mole ratio mixture of        bis(triethoxysilyl)ethane and tetraethoxysilane in the presence        of 0.1 molar hydrochloric acid to produce a polyorganosiloxane;    -   b) preparing an aqueous suspension of said        polyorganoalkoxysiloxane, said suspension further comprising the        surfactant Triton X-100, and gelling said suspension in the        presence of a ammonium hydroxide so as to produce porous hybrid        particles;    -   c) modifying the pore structure of said porous hybrid particles        by hydrothermal treatment at 155° C. for 20 h in 0.3 M        tris(hydroxymethyl)aminomethane, pH adjusted to 9.80;    -   d) sizing to a nominal 2 μm particle diameter;    -   e) acid washing in a 1 molar hydrochloric acid solution;    -   f) further surface modifying with octadecyltrichlorosilane        wherein any free silanol groups remaining from said surface        modification are endcapped with chlorotrimethylsilane; and    -   g) coalescing said porous hybrid particles to form a monolith        material.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material having a chromatographically-enhancing pore geometryand a formula SiO₂/[CH₃SiO_(1.5)]_(0.5) wherein said hybrid material hasbeen surface modified with octadecyltrichlorosilane and wherein any freesilanol groups remaining from said surface modification procedure areendcapped with chlorotrimethylsilane and wherein said material containsa plurality of macropores sufficient to result in reduced backpressureat chromatographically-useful flow rates.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material having a chromatographically-enhancing pore geometryand a formula SiO₂/[CH₃SiO_(1.5)]_(0.5), produced by the process of

-   -   a) preparing an aqueous solution of methyltrimethoxysilane and a        tetramethoxysilane in the presence of a 0.07 molar acetic acid        solution and the surfactant Pluronic P-105 or Trition X-100 to        produce a polyorganoalkoxysiloxane;    -   b) incubating said solution for 3 days at 45° C., resulting in a        three-dimensional gel having a continuous, interconnected pore        structure;    -   c) aging the gel in 1 molar ammonium hydroxide at 60° C. for 3        days to yield a solid monolith material;    -   d) rinsing the monolith material with water;    -   e) modifying the pore structure of said monolith material by        hydrothermal treatment at 155° C. for 20 h in 0.1 molar        tris(hydroxymethyl)aminomethane, pH adjusted to 8.0;    -   f) rinsing the monolith material with water followed by a        solvent exchange;    -   g) acid washing the monolith material in 1 molar hydrochloric        acid for 24 hours at 98° C.;    -   h) rinsing the monolith material with water followed by a        solvent exchange;    -   i) drying the monolith material at room temperature drying and        at 80° C. under vacuum; and    -   j) further surface modifying with octadecyltrichlorosilane        wherein any free silanol groups remaining from said surface        modification are endcapped with chlorotrimethylsilane.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material having a chromatographically-enhancing pore geometryand a formula SiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) wherein said hybridmaterial has been surface modified with octadecyltrichlorosilane andwherein any free silanol groups remaining from said surface modificationprocedure are endcapped with chlorotrimethylsilane and wherein saidmaterial contains a plurality of macropores sufficient to result inreduced backpressure at chromatographically-useful flow rates.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material having a chromatographically-enhancing pore geometryand a formula SiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25), produced by the process of

-   -   a) preparing an aqueous solution 1,2-bis(trimethoxysilyl)ethane        and tetramethoxysilane in the presence of a 0.09 molar acetic        acid solution and the surfactant Pluronic P-123 to produce a        polyorganoalkoxysiloxane;    -   b) incubating said solution for 2 days at 45° C., resulting in a        three-dimensional gel having a continuous, interconnected pore        structure;    -   c) aging the gel in 1 molar ammonium hydroxide at 60° C. for 2        days to yield a solid monolith material;    -   d) rinsing the monolith material with water;    -   e) modifying the pore structure of said monolith material by        hydrothermal treatment at 155° C. for 24 h in 0.1 M        tris(hydroxymethyl)aminomethane, pH adjusted to 10.6;    -   f) rinsing the monolith material with water followed by a        solvent exchange;    -   g) acid washing the monolith material in 1 molar hydrochloric        acid for 24 hours at 98° C.;    -   h) rinsing the monolith material with water followed by a        solvent exchange;    -   i) drying the monolith material at room temperature drying and        at 80° C. under vacuum, and    -   j) further surface modifying with octadecyltrichlorosilane        wherein any free silanol groups remaining from said surface        modification are endcapped with chlorotrimethylsilane.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material having a chromatographically-enhancing pore geometryand a formula SiO₂/[HOC₃H₆SiO_(1.5)]_(0.15) wherein said hybrid materialhas been surface modified with dodecylsiocyante and wherein saidmaterial contains a plurality of macropores sufficient to result inreduced backpressure at chromatographically-useful flow rates.

Another aspect of the invention is a porous inorganic/organic hybridmonolith material having a chromatographically-enhancing pore geometryand a formula SiO₂/[HOC₃H₆SiO_(1.5)]_(0.15), produced by the process of

-   -   a) preparing an aqueous solution        methacryloxypropyltrimethoxysilane and tetramethoxysilane in the        presence of a 0.015 molar acetic acid solution and the        surfactant Triton X-100 or Triton 405 to produce a        polyorganoalkoxysiloxane;    -   b) incubating said solution for 3 days at 45° C., resulting in a        three-dimensional gel having a continuous, interconnected pore        structure;    -   c) aging the gel in 1 molar ammonium hydroxide at 60° C. for 3        days to yield a solid monolith material;    -   d) rinsing the monolith material with water;    -   e) modifying the pore structure of said monolith material by        hydrothermal treatment at 155° C. for 24 h in 0.1 M        tris(hydroxymethyl)aminomethane, pH adjusted to 10.6;    -   f) rinsing the monolith material with water followed by a        solvent exchange;    -   g) acid washing the monolith material in 1 molar hydrochloric        acid for 24 hours at 98° C.;    -   h) rinsing the monolith material with water followed by a        solvent exchange;    -   i) drying the monolith material at room temperature drying and        at 80° C. under vacuum, and    -   j) further surface modifying with dodecylisocyanate.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 indicates the pressure change before and after the sintering andwashing steps described in Example 28 below as a function of the amountof unbonded silica used in the original mixture.

FIG. 2 demonstrates that the hydrothermal process described in Example32 below narrowed the mesopore size distribution.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be more fully illustrated by reference to thedefinitions set forth below.

The term “monolith” is intended to include a porous, three-dimensionalmaterial having a continuous interconnected pore structure in a singlepiece. A monolith is prepared, for example, by casting precursors into amold of a desired shape. The term monolith is meant to be distinguishedfrom a collection of individual particles packed into a bed formation,in which the end product comprises individual particles.

The terms “coalescing” and “coalesced” are intended to describe amaterial in which several individual components have become coherent toresult in one new component by an appropriate chemical or physicalprocess, e.g., heating. The term coalesced is meant to be distinguishedfrom a collection of individual particles in close physical proximity,e.g., in a bed formation, in which the end product comprises individualparticles.

The term “incubation” is intended to describe the time period during thepreparation of the inorganic/organic hybrid monolith material in whichthe precursors begin to gel.

The term “aging” is intended to describe the time period during thepreparation of the inorganic/organic hybrid monolith material in which asolid rod of monolithic material is formed.

The term “macropore” is intended to include pores of a material thatallow liquid to flow directly through the material with reducedresistance at chromatographically-useful flow rates. For example,macropores of the present invention are intended to include, but are notlimited to pores with a pore diameter larger than about 0.05 μm, poreswith a pore diameter ranging from about 0.05 μm to about 100 μm, poreswith a pore diameter ranging from about 0.11 μm to about 100 μm, andpores with a pore diameter ranging from about 0.5 μm to about 30 μm.

The term “chromatographically-useful flow rates” is intended to includeflow rates that one skilled in the art of chromatography would use inthe process of chromatography.

The language “chromatographically-enhancing pore geometry” includes thegeometry of the pore configuration of the presently-disclosed porousinorganic/organic hybrid materials, which has been found to enhance thechromatographic separation ability of the material, e.g., asdistinguished from other chromatographic media in the art. For example,a geometry can be formed, selected or constructed, and variousproperties and/or factors can be used to determine whether thechromatographic separations ability of the material has been “enhanced”,e.g., as compared to a geometry known or conventionally used in the art.Examples of these factors include high separation efficiency, longercolumn life, and high mass transfer properties (as evidenced by, e.g.,reduced band spreading and good peak shape.) These properties can bemeasured or observed using art-recognized techniques. For example, thechromatographically-enhancing pore geometry of the present porousinorganic/organic hybrid particles is distinguished from the prior artparticles by the absence of “ink bottle” or “shell shaped” pore geometryor morphology, both of which are undesirable because they, e.g., reducemass transfer rates, leading to lower efficiencies.

Chromatographically-enhancing pore geometry is found in hybridmaterials, e.g., particles or monoliths, containing only a smallpopulation of micropores and a sufficient population of mesopores. Asmall population of micropores is achieved in hybrid materials when allpores of a diameter of about <34 Å contribute less than about 110 m²/gto the specific surface area of the material. Hybrid materials with sucha low micropore surface area give chromatographic enhancements includinghigh separation efficiency and good mass transfer properties (asevidenced by, e.g., reduced band spreading and good peak shape).Micropore surface area is defined as the surface area in pores withdiameters less than or equal to 34 Å, determined by mulitpoint nitrogensorption analysis from the adsorption leg of the isotherm using the BJHmethod.

A sufficient population of mesopores is achieved in hybrid materialswhen all pores of a diameter of about 35 Å to about 500 Å, e.g.,preferably about 60 Å to about 500 Å, e.g., even more preferably about100 Å to about 300 Å, sufficiently contribute to the specific surfacearea of the material, e.g., to about 35 to about 750 m²/g, e.g.,preferably about 65-550 m²/g, e.g., even more preferably about 100 to350 m²/g to the specific surface area of the material.

“Hybrid”, i.e., as in “porous inorganic/organic hybrid particles” or“porous inorganic/organic hybrid monolith” includes inorganic-basedstructures wherein an organic functionality is integral to both theinternal or “skeletal” inorganic structure as well as the hybridmaterial surface. The inorganic portion of the hybrid material may be,e.g., alumina, silica, titanium or zirconium oxides, or ceramicmaterial; in a preferred embodiment, the inorganic portion of the hybridmaterial is silica. In a preferred embodiment where the inorganicportion is silica, “hybrid silica” refers to a material having theformula SiO₂/(R² _(p)R⁴ _(q)SiO_(t))_(n) or SiO₂/[R⁶(R²_(r)SiO_(t))_(m)]_(n) wherein R² and R⁴ are independently C₁-C₁₈aliphatic styryl, vinyl, propanol, or aromatic moieties (which mayadditionally be substituted with alkyl, aryl, cyano, amino, hydroxyl,diol, nitro, ester, ion exchange or embedded polar functionalities), R⁶is a substituted or unsubstituted C₁-C₁₈ alkylene, alkenylene,alkynylene or arylene moiety bridging two or more silicon atoms, p and qare 0, 1 or 2, provided that p+q=1 or 2, and that when p+q=1, t=1.5, andwhen p+q=2, t=1; r is 0 or 1, provided that when r=0, t=1.5, and whenr=1, t=1; m is an integer greater than or equal to 2, and n is a numberfrom 0.03 to 1, more preferably, 0.1 to 1, and even more preferably 0.2to 0.5. R² may be additionally substituted with a functionalizing groupR.

The term “functionalizing group” includes organic groups which impart acertain chromatographic functionality to a chromatographic stationaryphase, including, e.g., octadecyl (C₁₈) or phenyl. Such functionalizinggroups are present in, e.g., surface modifiers such as disclosed hereinwhich are attached to the base material, e.g., via derivatization orcoating and later crosslinking, imparting the chemical character of thesurface modifier to the base material. In an embodiment, such surfacemodifiers have the formula Z_(a)(R′)_(b)Si—R, where Z═Cl, Br, I, C₁-C₅alkoxy, dialkylamino, e.g., dimethylamino, or trifluoromethanesulfonate;a and b are each an integer from 0 to 3 provided that a+b=3; R′ is aC₁-C₆ straight, cyclic or branched alkyl group, and R is afunctionalizing group. R′ may be, e.g., methyl, ethyl, propyl,isopropyl, butyl, t-butyl, sec-butyl, pentyl, isopentyl, hexyl orcyclohexyl; preferably, R′ is methyl.

The porous inorganic/organic hybrid particles and monolith materialspossess both organic groups and silanol groups which may additionally besubstituted or derivatized with a surface modifier. “Surface modifiers”include (typically) organic groups which impart a certainchromatographic functionality to a chromatographic stationary phase.Surface modifiers such as disclosed herein are attached to the basematerial, e.g., via derivatization or coating and later crosslinking,imparting the chemical character of the surface modifier to the basematerial. In one embodiment, the organic groups of the hybrid materialsreact to form an organic covalent bond with a surface modifier. Themodifiers can form an organic covalent bond to the material's organicgroup via a number of mechanisms well known in organic and polymerchemistry including but not limited to nucleophilic, electrophilic,cycloaddition, free-radical, carbene, nitrene, and carbocationreactions. Organic covalent bonds are defined to involve the formationof a covalent bond between the common elements of organic chemistryincluding but not limited to hydrogen, boron, carbon, nitrogen, oxygen,silicon, phosphorus, sulfur, and the halogens. In addition,carbon-silicon and carbon-oxygen-silicon bonds are defined as organiccovalent bonds, whereas silicon-oxygen-silicon bonds that are notdefined as organic covalent bonds. In general, the porousinorganic/organic hybrid particles and monolith materials can bemodified by an organic group surface modifier, a silanol group surfacemodifier, a polymeric coating surface modifier, and combinations of theaforementioned surface modifiers.

For example, silanol groups are surface modified with compounds havingthe formula Z_(a)(R′)_(b)Si—R, where Z═Cl, Br, I, C₁-C₅ alkoxy,dialkylamino, e.g., dimethylamino, or trifluoromethanesulfonate; a and bare each an integer from 0 to 3 provided that a+b=3; R′ is a C₁-C₆straight, cyclic or branched alkyl group, and R is a functionalizinggroup. R′ may be, e.g., methyl, ethyl, propyl, isopropyl, butyl,t-butyl, sec-butyl, pentyl, isopentyl, hexyl or cyclohexyl; preferably,R′ is methyl. In certain embodiments, the organic groups may besimilarly functionalized.

The functionalizing group R may include alkyl, aryl, cyano, amino, diol,nitro, cation or anion exchange groups, or embedded polarfunctionalities. Examples of suitable R functionalizing groups includeC₁-C₃₀ alkyl, including C₁-C₂₀, such as octyl (C₈), octadecyl (C₁₈), andtriacontyl (C₃₀); alkaryl, e.g., C₁-C₄-phenyl; cyanoalkyl groups, e.g.,cyanopropyl; diol groups, e.g., propyldiol; amino groups, e.g.,aminopropyl; and alkyl or aryl groups with embedded polarfunctionalities, e.g., carbamate functionalities such as disclosed inU.S. Pat. No. 5,374,755, the text of which is incorporated herein byreference. Such groups include those of the general formula

wherein l, m, o, r, and s are 0 or 1, n is 0, 1, 2 or 3 p is 0, 1, 2, 3or 4 and q is an integer from 0 to 19; R₃ is selected from the groupconsisting of hydrogen, alkyl, cyano and phenyl; and Z, R′, a and b aredefined as above. Preferably, the carbamate functionality has thegeneral structure indicated below:

wherein R⁵ may be, e.g., cyanoalkyl, t-butyl, butyl, octyl, dodecyl,tetradecyl, octadecyl, or benzyl. Advantageously, R⁵ is octyl, dodecyl,or octadecyl.

In a preferred embodiment, the surface modifier may be anorganotrihalosilane, such as octyltrichlorosilane oroctadecyltrichlorosilane. In an additional preferred embodiment, thesurface modifier may be a halopolyorganosilane, such asoctyldimethylchlorosilane or octadecyldimethylchlorosilane. In certainembodiments the surface modifier is octadecyltrimethoxysilane.

In another embodiment, the hybrid material's organic groups and silanolgroups are both surface modified or derivatized. In another embodiment,the hybrid materials are surface modified by coating with a polymer.

The term “aliphatic group” includes organic compounds characterized bystraight or branched chains, typically having between 1 and 22 carbonatoms. Aliphatic groups include alkyl groups, alkenyl groups and alkynylgroups. In complex structures, the chains can be branched orcross-linked. Alkyl groups include saturated hydrocarbons having one ormore carbon atoms, including straight-chain alkyl groups andbranched-chain alkyl groups. Such hydrocarbon moieties may besubstituted on one or more carbons with, for example, a halogen, ahydroxyl, a thiol, an amino, an alkoxy, an alkylcarboxy, an alkylthio,or a nitro group. Unless the number of carbons is otherwise specified,“lower aliphatic” as used herein means an aliphatic group, as definedabove (e.g., lower alkyl, lower alkenyl, lower alkynyl), but having fromone to six carbon atoms. Representative of such lower aliphatic groups,e.g., lower alkyl groups, are methyl, ethyl, n-propyl, isopropyl,2-chloropropyl, n-butyl, sec-butyl, 2-aminobutyl, isobutyl, tert-butyl,3-thiopentyl, and the like. As used herein, the term “nitro” means—NO₂;the term “halogen” designates —F, —Cl, —Br or —I; the term “thiol” meansSH; and the term “hydroxyl” means —OH. Thus, the term “alkylamino” asused herein means an alkyl group, as defined above, having an aminogroup attached thereto. Suitable alkylamino groups include groups having1 to about 12 carbon atoms, preferably from 1 to about 6 carbon atoms.The term “alkylthio” refers to an alkyl group, as defined above, havinga sulfhydryl group attached thereto. Suitable alkylthio groups includegroups having 1 to about 12 carbon atoms, preferably from 1 to about 6carbon atoms. The term “alkylcarboxyl” as used herein means an alkylgroup, as defined above, having a carboxyl group attached thereto. Theterm “alkoxy” as used herein means an alkyl group, as defined above,having an oxygen atom attached thereto. Representative alkoxy groupsinclude groups having 1 to about 12 carbon atoms, preferably 1 to about6 carbon atoms, e.g., methoxy, ethoxy, propoxy, tert-butoxy and thelike. The terms “alkenyl” and “alkynyl” refer to unsaturated aliphaticgroups analogous to alkyls, but which contain at least one double ortriple bond respectively. Suitable alkenyl and alkynyl groups includegroups having 2 to about 12 carbon atoms, preferably from 1 to about 6carbon atoms.

The term “alicyclic group” includes closed ring structures of three ormore carbon atoms. Alicyclic groups include cycloparaffins or naphtheneswhich are saturated cyclic hydrocarbons, cycloolefins which areunsaturated with two or more double bonds, and cycloacetylenes whichhave a triple bond. They do not include aromatic groups. Examples ofcycloparaffins include cyclopropane, cyclohexane, and cyclopentane.Examples of cycloolefins include cyclopentadiene and cyclooctatetraene.Alicyclic groups also include fused ring structures and substitutedalicyclic groups such as alkyl substituted alicyclic groups. In theinstance of the alicyclics such substituents can further comprise alower alkyl, a lower alkenyl, a lower alkoxy, a lower alkylthio, a loweralkylamino, a lower alkylcarboxyl, a nitro, a hydroxyl, —CF₃, —CN, orthe like.

The term “heterocyclic group” includes closed ring structures in whichone or more of the atoms in the ring is an element other than carbon,for example, nitrogen, sulfur, or oxygen. Heterocyclic groups can besaturated or unsaturated and heterocyclic groups such as pyrrole andfuran can have aromatic character. They include fused ring structuressuch as quinoline and isoquinoline. Other examples of heterocyclicgroups include pyridine and purine. Heterocyclic groups can also besubstituted at one or more constituent atoms with, for example, ahalogen, a lower alkyl, a lower alkenyl, a lower alkoxy, a loweralkylthio, a lower alkylamino, a lower alkylcarboxyl, a nitro, ahydroxyl, —CF₃, —CN, or the like. Suitable heteroaromatic andheteroalicyclic groups generally will have 1 to 3 separate or fusedrings with 3 to about 8 members per ring and one or more N, O or Satoms, e.g. coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl,furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl,benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl,piperidinyl, morpholino and pyrrolidinyl.

The term “aromatic group” includes unsaturated cyclic hydrocarbonscontaining one or more rings. Aromatic groups include 5- and 6-memberedsingle-ring groups which may include from zero to four heteroatoms, forexample, benzene, pyrrole, furan, thiophene, imidazole, oxazole,thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine andpyrimidine, and the like. The aromatic ring may be substituted at one ormore ring positions with, for example, a halogen, a lower alkyl, a loweralkenyl, a lower alkoxy, a lower alkylthio, a lower alkylamino, a loweralkylcarboxyl, a nitro, a hydroxyl, —CF₃, —CN, or the like.

The term “alkyl” includes saturated aliphatic groups, includingstraight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl(alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkylsubstituted alkyl groups. In certain embodiments, a straight chain orbranched chain alkyl has 30 or fewer carbon atoms in its backbone, e.g.,C₁-C₃₀ for straight chain or C₃-C₃₀ for branched chain. In certainembodiments, a straight chain or branched chain alkyl has 20 or fewercarbon atoms in its backbone, e.g., C₁-C₂₀ for straight chain or C₃-C₂₀for branched chain, and more preferably 18 or fewer. Likewise, preferredcycloalkyls have from 4-10 carbon atoms in their ring structure, andmore preferably have 4-7 carbon atoms in the ring structure. The term“lower alkyl” refers to alkyl groups having from 1 to 6 carbons in thechain, and to cycloalkyls having from 3 to 6 carbons in the ringstructure.

Moreover, the term “alkyl” (including “lower alkyl”) as used throughoutthe specification and claims includes both “unsubstituted alkyls” and“substituted alkyls”, the latter of which refers to alkyl moietieshaving substituents replacing a hydrogen on one or more carbons of thehydrocarbon backbone. Such substituents can include, for example,halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy,aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl,aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato,phosphinato, cyano, amino (including alkyl amino, dialkylamino,arylamino, diarylamino, and alkylarylamino), acylamino (includingalkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino,imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfate,sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido,heterocyclyl, aralkyl, or an aromatic or heteroaromatic moiety. It willbe understood by those skilled in the art that the moieties substitutedon the hydrocarbon chain can themselves be substituted, if appropriate.Cycloalkyls can be further substituted, e.g., with the substituentsdescribed above. An “aralkyl” moiety is an alkyl substituted with anaryl, e.g., having 1 to 3 separate or fused rings and from 6 to about 18carbon ring atoms, e.g., phenylmethyl (benzyl).

The term “aryl” includes 5- and 6-membered single-ring aromatic groupsthat may include from zero to four heteroatoms, for example,unsubstituted or substituted benzene, pyrrole, furan, thiophene,imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine,pyridazine and pyrimidine, and the like. Aryl groups also includepolycyclic fused aromatic groups such as naphthyl, quinolyl, indolyl,and the like. The aromatic ring can be substituted at one or more ringpositions with such substituents, e.g., as described above for alkylgroups. Suitable aryl groups include unsubstituted and substitutedphenyl groups. The term “aryloxy” as used herein means an aryl group, asdefined above, having an oxygen atom attached thereto. The term“aralkoxy” as used herein means an aralkyl group, as defined above,having an oxygen atom attached thereto. Suitable aralkoxy groups have 1to 3 separate or fused rings and from 6 to about 18 carbon ring atoms,e.g., O-benzyl.

The term “amino,” as used herein, refers to an unsubstituted orsubstituted moiety of the formula —NR_(a)R_(b), in which R_(a) and R_(b)are each independently hydrogen, alkyl, aryl, or heterocyclyl, or R_(a)and R_(b), taken together with the nitrogen atom to which they areattached, form a cyclic moiety having from 3 to 8 atoms in the ring.Thus, the term “amino” includes cyclic amino moieties such aspiperidinyl or pyrrolidinyl groups, unless otherwise stated. An“amino-substituted amino group” refers to an amino group in which atleast one of R_(a) and R_(b), is further substituted with an aminogroup.

The present porous inorganic/organic hybrid materials having achromatographically-enhancing pore geometry generally have a specificsurface area, as measured by N₂ sorption analysis, of about 50 to 800m²/g, preferably about 75 to 600 m²/g, more preferably about 100 to 350m²/g. The specific pore volume of the hybrid materials is generallyabout 0.25 to 1.5 cm³/g, preferably about 0.4 to 1.2 cm³/g, morepreferably about 0.5 to 1.0 cm³/g. The porous inorganic/organic hybridmaterials having a chromatographically-enhancing pore geometry have anaverage pore diameter of generally about 50 to 500 Å, preferably about60 to 500 Å, more preferably about 100 to 300 Å. The micropore surfacearea is less than about 110 m²/g, preferably less than about 105 m²/g,more preferably less than about 80 m²/g, and still more preferably lessthan about 50 m²/g.

Porous inorganic/organic hybrid materials having achromatographically-enhancing pore geometry may be made as describedbelow and in the specific instances illustrated in the Examples. Porousspherical particles of hybrid silica may, in one embodiment, be preparedby a multi-step process. In the first step, one or moreorganoalkoxysilanes such as methyltriethoxysilane, and atetraalkoxysilane such as tetraethoxysilane (TEOS) are prepolymerized toform a polyorganoalkoxysiloxane (POS), e.g., polyalkylalkoxysiloxane, byco-hydrolyzing a mixture of the two or more components in the presenceof an acid catalyst. In the second step, the POS is suspended in anaqueous medium in the presence of a surfactant or a combination ofsurfactants and gelled into porous spherical particles of hybrid silicausing a base catalyst. In the third step, the pore structure of thehybrid silica particles is modified by hydrothermal treatment, producingan intermediate hybrid silica product which may be used for particularpurposes itself, or desirably may be further processed, as describedbelow. The above three steps of the process allow much better control ofthe particle sphericity, morphology, pore volume and pore sizes thanthose described in the prior art, and thus provide thechromatographically-enhancing pore geometry.

In one embodiment of the invention, the surface organic groups of thehybrid silica are derivatized or modified in a subsequent step viaformation of an organic covalent bond between the particle's organicgroup and the modifying reagent. Alternatively, the surface silanolgroups of the hybrid silica are derivatized into siloxane organicgroups, such as by reacting with an organotrihalosilane, e.g.,octadecyltrichlorosilane, or a halopolyorganosilane, e.g.,octadecyldimethylchlorosilane. Alternatively, the surface organic andsilanol groups of the hybrid silica are both derivatized. The surface ofthe thus-prepared material is then covered by the organic groups, e.g.,alkyl, embedded during the gelation and the organic groups added duringthe derivatization process or processes. The surface coverage by theoverall organic groups is higher than in conventional silica-basedpacking materials, and therefore the surface concentration of theremaining silanol groups in the hybrid silica is smaller. The resultingmaterial, used as a stationary phase for LC, shows excellent peak shapefor basic analytes, and better stability to alkaline mobile phases thansilica-based packing materials.

Where the prepolymerization step involves co-hydrolyzing a mixture ofthe two or more components in the presence of an acid catalyst, thecontent of the organoalkoxysilane, e.g., organotrialkoxysilane, can bevaried, e.g., from about 0.03 to about 1.0 mole per mole, or morepreferably, about 0.2 to about 0.5 mole per mole, of thetetraalkoxysilane. The amount of the water used for the hydrolysis canbe varied, e.g., from about 1.10 to about 1.35 mole per mole of thesilane. The silane, water and the ethanol mixture, in the form of ahomogeneous solution, is stirred and heated to reflux under a flow ofargon. After it is refluxed for a time sufficient to prepolymerize toform polyorganoalkoxysiloxane (POS), e.g., polyalkylalkoxysiloxane, thesolvent and the side product, mainly ethanol, is distilled off from thereaction mixture. Thereafter, the residue is heated at an elevatedtemperature, e.g., in the range of about 120 to 140° C. under anatmosphere of argon for a period of time, e.g., about 1.5 to 16 h. Theresidue is further heated at this temperature, e.g., for about 1 to 3 hunder reduced pressure, e.g., about 10⁻² to 10⁻³ torr, to remove anyvolatile species.

In the second step, the POS is suspended into fine beads in a solutioncontaining water and ethanol at 55° C. by agitation. The volume percentof ethanol in the solution is varied from 10 to 20%. A non-ionicsurfactant such as Triton X-100 or Triton X-45 is added into thesuspension as the suspending agent. Alternatively a mixture of TritonX-45 and low levels of sodium dodecyl sulfate (SDS) ortris(hydroxymethyl)aminomethane lauryl sulfate (TDS) is added into thesuspension as the suspending agent. The surfactants, e.g.,alkylphenoxypolyethoxyethanol, are believed to be able to orient at thehydrophobic/hydrophilic interface between the POS beads and the aqueousphase to stabilize the POS beads. The surfactants are also believed toenhance the concentration of water and the base catalyst on the surfaceof the POS beads during the gelation step, through their hydrophilicgroups, which induces the gelling of the POS beads from the surfacetowards the center. Use of surfactants to modulate the surface structureof the POS beads stabilizes the shape of the POS beads throughout thegelling process, and minimizes or suppresses formation of particleshaving irregular shapes, e.g., “shell shaped”, and inhomogeneousmorphology.

It is also possible to suspend a solution containing POS and toluene inthe aqueous phase, instead of POS alone. The toluene, which is insolublein the aqueous phase, remains in the POS beads during the gelation stepand functions as a porogen. By controlling the relative amount oftoluene in the POS/toluene solution, the pore volume of the final hybridsilica can be more precisely controlled. This allows the preparation ofhybrid silica particles having large pore volume, e.g., 0.8-1.2 cm³/g.

The gelation step is initiated by adding a basic catalyst, e.g.,ammonium hydroxide into the POS suspension agitated at 55° C.Thereafter, the reaction mixture is agitated at the same temperature todrive the reaction to completion Ammonium hydroxide is preferred becausebases such as sodium hydroxide are a source of unwanted cations, andammonium hydroxide is easier to remove in the washing step. Thethus-prepared hybrid silica is filtered and washed with water andmethanol that are free of ammonium ions, then dried.

In one embodiment, the pore structure of the as-prepared hybrid materialis modified by hydrothermal treatment, which enlarges the openings ofthe pores as well as the pore diameters, as confirmed by nitrogen (N₂)sorption analysis. The hydrothermal treatment is performed by preparinga slurry containing the as-prepared hybrid material and a solution oforganic base in water, heating the slurry in an autoclave at an elevatedtemperature, e.g., about 143 to 168° C., for a period of about 6 to 28h. The pH of the slurry can be adjusted to be in the range of about 8.0to 10.7 using concentrated acetic acid. The concentration of the slurryis in the range of about 1 g hybrid material per 5 to 10 mL of the basesolution. The thus-treated hybrid material is filtered, and washed withwater until the pH of the filtrate reaches about 7, washed with acetone,then dried at about 100° C. under reduced pressure for about 16 h. Theresultant hybrid materials show average pore diameters in the range ofabout 100-300 Å. The surface of the hydrothermally treated hybridmaterial may be modified in a similar fashion to that of the hybridmaterial that is not modified by hydrothermal treatment as described inthe present invention.

Moreover, the surface of the hydrothermally treated hybrid silicacontains organic groups, which can be derivatized by reacting with areagent that is reactive towards the hybrid materials' organic group.For example, vinyl groups on the material can be reacted with a varietyof olefin reactive reagents such as bromine (Br₂), hydrogen (H₂), freeradicals, propagating polymer radical centers, dienes, and the like. Inanother example, hydroxyl groups on the material can be reacted with avariety of alcohol reactive reagents such as isocyanates, carboxylicacids, carboxylic acid chlorides, and reactive organosilanes asdescribed below. Reactions of this type are well known in theliterature, see, e.g., March, J. “Advanced Organic Chemistry,” 3^(rd)Edition, Wiley, New York, 1985; Odian, G. “The Principles ofPolymerization,” 2^(nd) Edition, Wiley, New York, 1981; the texts ofwhich are incorporated herein by reference.

In addition, the surface of the hydrothermally treated hybrid silicaalso contains silanol groups, which can be derivatized by reacting witha reactive organosilane. The surface derivatization of the hybrid silicais conducted according to standard methods, for example by reaction withoctadecyltrichlorosilane or octadecyldimethylchlorosilane in an organicsolvent under reflux conditions. An organic solvent such as toluene istypically used for this reaction. An organic base such as pyridine orimidazole is added to the reaction mixture to catalyze the reaction. Theproduct of this reaction is then washed with water, toluene and acetoneand dried at about 80° C. to 100° C. under reduced pressure for about 16h. The resultant hybrid silica can be further reacted with a short-chainsilane such as trimethylchlorosilane to endcap the remaining silanolgroups, by using a similar procedure described above.

More generally, the surface of the hybrid silica materials may besurface modified with a surface modifier, e.g., Z_(a)(R′)_(b)Si—R, whereZ═Cl, Br, I, C₁-C₅ alkoxy, dialkylamino, e.g., dimethylamino, ortrifluoromethanesulfonate; a and b are each an integer from 0 to 3provided that a+b=3; R′ is a C₁-C₆ straight, cyclic or branched alkylgroup, and R is a functionalizing group. R′ may be, e.g., methyl, ethyl,propyl, isopropyl, butyl, t-butyl, sec-butyl, pentyl, isopentyl, hexylor cyclohexyl; preferably, R′ is methyl.

The functionalizing group R may include alkyl, alkenyl, alkynyl, aryl,cyano, amino, diol, nitro, cation or anion exchange groups, or alkyl oraryl groups with embedded polar functionalities. Examples of suitable Rfunctionalizing groups include C₁-C₃₀ alkyl, including C₁-C₂₀, such asoctyl (C₈₋), octadecyl (C₁₈₋), and triacontyl (C₃₀₋); alkaryl, e.g.,C₁-C₄-phenyl; cyanoalkyl groups, e.g., cyanopropyl; diol groups, e.g.,propyldiol; amino groups, e.g., aminopropyl; and alkyl or aryl groupswith embedded polar functionalities, e.g., carbamate functionalitiessuch as disclosed in U.S. Pat. No. 5,374,755, the text of which isincorporated herein by reference and as detailed hereinabove. In apreferred embodiment, the surface modifier may be anorganotrihalosilane, such as octyltrichlorosilane oroctadecyltrichlorosilane. In an additional preferred embodiment, thesurface modifier may be a halopolyorganosilane, such asoctyldimethylchlorosilane or octadecyldimethylchlorosilane.Advantageously, R is octyl or octadecyl.

The surface of the hybrid silica materials may also be surface modifiedby coating with a polymer. Polymer coatings are known in the literatureand may be provided generally by polymerization or polycondensation ofphysisorbed monomers onto the surface without chemical bonding of thepolymer layer to the support (type I), polymerization orpolycondensation of physisorbed monomers onto the surface with chemicalbonding of the polymer layer to the support (type II), immobilization ofphysisorbed prepolymers to the support (type III), and chemisorption ofpresynthesized polymers onto the surface of the support (type IV). see,e.g., Hanson et al., J. Chromat. A656 (1993) 369-380, the text of whichis incorporated herein by reference. As noted above, coating the hybridmaterial with a polymer may be used in conjunction with various surfacemodifications described in the invention. In a preferred embodiment,Sylgard® is used as the polymer.

Another embodiment of the invention is a porous inorganic/organic hybridmonolith material. The hybrid monolith materials of the currentinvention may be indirectly prepared by coalescing the inorganic/organichybrid particles of the invention or may be directly prepared frominorganic and organic precursors. Because of the novel processes of theinvention, the hybrid monolith material of the invention have a highsurface coverage of organic groups, in addition to achromatographically-enhancing pore geometry. Furthermore, byincorporation of the organic moieties in the silica backbone, thehydrophobic properties of the hybrid monolith material, as is seen inthe hybrid particles of the invention, can be tailored to impartsignificantly improved alkaline stability.

Porous inorganic/organic hybrid monolith materials may be made asdescribed below and in the specific instances illustrated in theExamples. In a preferred embodiment, the porous spherical particles ofhybrid silica of the invention may be used as prepared by the processnoted above, without further modification. These hybrid particles aremixed with a second material, e.g., unbonded silica, and packed into acontainer, e.g., a column. After packing is complete, the mixture iscoalesced, e.g., sintered, and the second material is subsequentlyremoved by a washing step. The resulting monolith material is furtherprocessed, e.g., rinsed with a solvent, to result in the hybrid monolithmaterial.

Alternatively, the monolith material may be prepared directly by asol-gel process. Current sol-gel processes for inorganic monolithmaterials require a calcination step where the temperature reaches above400° C. This process is not suitable for hybrid monolith materials sincethe organic moieties can be destroyed. Furthermore, silanol groups canbe irreversibly condensed above 400° C., leaving behind more acidicsilanols. As a result, some analytes, particularly basic analytes, cansuffer from increased retention, excessive tailing and irreversibleadsorption. The unique sol-gel process of the current invention ofpreparing the inorganic/organic hybrid monolith materials at lowtemperature preserves the organic moieties in the monolith material andprecludes irreversible silanol condensation.

The general process for directly preparing an inorganic/organic hybridmonolith material in a single step from inorganic and organic precursorscan be characterized by the following process.

First, a solution is prepared containing an aqueous acid, e.g., acetic,with a surfactant, an inorganic precursor, e.g., a tetraalkoxysilane,and an organic precursor, e.g., a organoalkoxysilane, e.g.,organotrialkoxysilane. The range of acid concentration is from about 0.1mM to 500 mM, more preferably from about 10 mM to 150 mM, and still morepreferably from about 50 mM to 120 mM. The range of surfactantconcentration is between about 3% and 15% by weight, more preferablybetween about 7 and 12% by weight, and still more preferably betweenabout 8% to 10% by weight. Furthermore, the range of the total silaneconcentration, e.g., methyltrimethoxysilane and tetramethoxysilane,employed in the process is kept below about 5 g/ml, more preferablybelow 2 g/ml, and still more preferably below 1 g/ml.

The sol solution is then incubated at a controlled temperature,resulting in a three-dimensional gel having a continuous, interconnectedpore structure. The incubation temperature range is between about thefreezing point of the solution and 90° C., more preferably between about20° C. and 70° C., still more preferably between about 35° C. and 60° C.The gel is aged at a controlled pH, preferably about pH 2-3, andtemperature, preferably about 20-70° C., more preferably about 35 to 60°C., for about 5 hours to about 10 days, more preferably from about 10hours to about 7 days, and still more preferably from about 2 days toabout 5 days, to yield a solid monolith material.

In order to further gel the hybrid material and to remove surfactant,the monolith material is rinsed with an aqueous basic solution, e.g.,ammonium hydroxide, at an temperature of about 0° C. to 80° C., morepreferably between about 20° C. and 70° C., and still more preferablybetween about 40° C. and 60° C. Additionally, in certain embodiments,the concentration of base is between about 10⁻⁵N and 1 N, morepreferably between about 10⁻⁴ N and 0.5 N, and still more preferablybetween about 10⁻³ N and 0.1 N. The monolith material is rinsed forabout 1 to 6 days, more preferably for about 1.5 to 4.5 days, the stillmore preferably for about 2 to 3 days.

In addition, the monolith material may undergo hydrothermal treatment ina basic solution at an elevated temperature, e.g., in an autoclave, toimprove the monolith material's pore structure. The preferred pH of thehydrothermal treatment is between about 7.0 and 12.0, more preferablybetween about 7.3 and 11.0, and still more preferably between about 7.5and 10.6. The temperature of the hydrothermal treatment is between about110° C. and 180° C., more preferably between about 120° C. and 160° C.,and still more preferably between about 130° C. and 155° C. The monolithmaterial is then rinsed with water followed by a solvent exchange withmethanol, ethanol, acetonitrile, tetrahydrofuran, or hexane, and roomtemperature drying. The monolith material is then dried at about 70 to120° C., and preferably at about 100° C. under vacuum for about 16-24hours.

In a subsequent step, the surface organic groups of the hybrid monolithmaterial, prepared directly or indirectly, are optionally derivatized ormodified via formation of a covalent bond between the monolithmaterial's organic and/or silanol group and the modifying reagent,optionally including coating with a polymer, as is described for thehybrid particles.

The porous inorganic/organic hybrid monolith materials of the currentinvention have a wide variety of end uses in the separation sciences,such as materials for chromatographic columns (wherein such columns mayhave improved stability to alkaline mobile phases and reduced peaktailing for basic analytes), thin layer chromatographic (TLC) plates,filtration membranes, microtiter plates, scavenger resins, solid phaseorganic synthesis supports, and the like, having a stationary phase thatincludes porous inorganic/organic hybrid materials having achromatographically-enhancing pore geometry and porous inorganic/organichybrid monolith materials of the present invention. The stationary phasemay be introduced by packing, coating, impregnation, cladding, wrapping,or other art-recognized techniques, etc., depending on the requirementsof the particular device. In a particularly advantageous embodiment, thechromatographic device is a chromatographic column, such as commonlyused in HPLC.

EXAMPLES

The present invention may be further illustrated by the followingnon-limiting examples describing the preparation of porousinorganic/organic hybrid particles and monolith materials, and theiruse.

Example 1

An organoalkoxysilane and tetraethoxysilane (all from Gelest Inc.,Tullytown, Pa.) are mixed with ethanol (HPLC grade, J.T. Baker,Phillipsburgh, N.J.) and 0.1 N hydrochloric acid (Aldrich Chemical,Milwaukee, Wis.) in a flask. The resulting solution is agitated andrefluxed for 16 h in an atmosphere of argon or nitrogen. Ethanol andmethanol (if applicable) are removed from the flask via distillation atatmospheric pressure. Residual alcohol and volatile species are removedby heating at 115-140° C. for 1-2 h in a sweeping stream of inert gas orby heating at 125° C. under reduced pressure for 1-2 h. The resultingpolyorganoalkoxysiloxanes are colorless viscous liquids. The productnumbers and the respective chemical formula of theorganotrialkoxysilanes used in the copolymerization withtetraethoxysilane are listed in Table 1. The specific amounts ofstarting materials used to prepare these products are listed in Table 2.

TABLE 1 Used in Organoalkoxysilane Organic Group Products ChemicalFormula Name 1a, b, c CH₃Si(OCH₂CH₃)₃ methyl 1d C₂H₅Si(OCH₂CH₃)₃ ethyl1e C₆H₅Si(OCH₂CH₃)₃ phenyl 1f, g, h, i, j,(CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ ethane bridge 1k, l H₂C═CHSi(OCH₂CH₃)₃vinyl 1m, n, o H₂C═C(CH₃)CO₂C₃H₆Si(OCH₃)₃ methacryloxypropyl 1p, qH₂C═CHC₆H₄C₂H₄Si(OCH₃)₃ styrylethyl

TABLE 2 Organotri- 0.1N Mole Ratio: alkoxysilane TEOS HCl EthanolProduct Organosilane/TEOS (g) (g) (g) (mL) 1a 0.20 137 802 109 400 1b0.35 249 832 116 300 1c 0.50 534 1248 203 450 1d 0.25 116 503 65 300 1e0.25 113 392 53 300 1f 0.037 19 297 37 218 1g 0.125 59 278 39 218 1h0.25 106 250 40 218 1i 0.50 177 208 43 218 1j 1.0 266 156 46 218 1k 0.25160 875 119 253 1l 0.50 799 1750 297 736 1m 0.10 179 1500 178 463 1n0.125 373 2500 304 788 1o 0.25 671 2250 304 788 1p 0.033 15 355 42 99 1q0.10 20 156 19 47

Example 2

A mixture of a surfactant (Triton X-45 or Triton X-100, AldrichChemical, Milwaukee, Wis.), ethanol (anhydrous, J.T. Baker,Phillipsburgh, N.J.), and deionized water was heated at 55° C. for 0.5h, resulting in a white liquid. Under rapid agitation, a solution oftoluene (HPLC grade, J.T. Baker, Phillipsburgh, N.J.) inpolyorganalkoxysiloxane (selected from Table 2) was added into theethanol/water/Triton mixture, and emulsified in the aqueous phase.Thereafter, 30% NH₄OH (VWR, Bridgeport, N.J.) was added into theemulsion to gel the emulsion beads. Suspended in the solution, thegelled product was transferred to a flask and stirred at 55° C. for 16h. The resulting spherical, porous, hybrid inorganic/organic particleswere collected on 0.5 μm filtration paper and washed successively withwater and methanol (HPLC grade, J.T. Baker, Phillipsburgh, N.J.). Theproducts were then dried in a vacuum oven at 80° C. overnight. Specificamounts of starting materials used to prepare these products are listedin Table 3. ¹³C and ²⁹Si CPMAS NMR spectra of the products areconsistent with the assigned products with respect to organic groupstructure and ratio of organic/inorganic units. For products, 2q, 2r,and 2s, approximately 30% of the methacryoxypropyl ester groups wereobserved to hydrolyze to the corresponding 3-hydroxypropyl organic unitand methacrylic acid, where the acid was removed in the wash steps.

Example 3

A mixture of Triton X-45 and sodium dodecylsulfate (SDS) (J.T. Baker,Phillipsburgh, N.J.) or tris(hydroxymethyl)aminomethane lauryl sulfate(TDS) (Fluka Chemical, Milwaukee, Wis.) was used to prepare spherical,porous, hybrid inorganic/organic particles made from thepolyorganoalkoxysiloxanes consisting of bis(triethoxysilyl)ethane/TEOSmolar ratios of 0.5 and 1.0 (Table 2, products 1i and 1j, respectively).The procedure was the same as described for Example 2, except that the30% NH₄OH was added to the emulsion after transfer from the emulsifierreactor to the stirred reaction flask. The molar ratio of TritonX-45/SDS or TDS was 1.2/1.0. The specific amounts of reagents used toprepare these products (2l, 2m, 2n) are listed in Table 3.

TABLE 3 Polyorgano- Mole Ratio: Ammonium alkoxysilaneOrganosiloxane/SiO₂ Polyorgano- Toluene Ethanol Water SurfactantSurfactant Hydroxide Product Feedstock in product alkoxysilane (g) (mL)(mL) (mL) Type (g) (mL) 2a 1a 0.20 240 0 240 960 X-100 20 150 2b 1c 0.50240 0 240 960 X-100 20 150 2c 1a 0.20 249 30 285 1200 X-45 24 190 2d 1b0.35 249 30 285 1200 X-45 24 190 2e 1c 0.50 249 30 285 1200 X-45 24 1902f 1c 0.50 249 60 285 1200 X-45 24 190 2g 1d 0.25 240 0 240 960 X-100 20150 2h 1e 0.25 240 0 240 960 X-100 20 150 2i 1f 0.037 58 7.0 66 280 X-455.6 44 2j 1g 0.125 500 70 660 2800 X-45 56 440 2k 1h 0.25 580 70 6602800 X-45 56 440 2l 1i 0.50 58 7.0 66 280 X-45/SDS 5.6 44 2m 1i 0.50 587.0 66 280 X-45/TDS 5.6 44 2n 1j 1.0 58 7.0 66 280 X-45/SDS 5.6 44 2o 1k0.25 436 53 482 2100 X-45 42 362 2p 1l 0.50 479 58 530 2310 X-45 46 3982q 1m 0.10 479 58 530 2310 X-45 46 398 2r 1n 0.125 53 6.5 59 257 X-455.2 44 2s 1o 0.25 53 6.5 59 257 X-45 5.2 44 2t 1p 0.033 202 25 223 973X-45 19.5 168 2u 1q 0.10 53 6.6 59 257 X-45 5.1 44

Example 4

Spherical, porous, hybrid inorganic/organic particles of Examples 2 and3 were mixed with tris(hydroxymethyl)aminomethane (TRIS, AldrichChemical, Milwaukee, Wis.) in water, yielding a slurry. The pH of theslurry was adjusted as necessary to between 8 and 10.7 by addingconcentrated acetic acid. The resultant slurry was then enclosed in astainless steel autoclave and heated to between 140 and 165° C. for 20h. After the autoclave cooled to room temperature the product wasfiltered and washed repeatedly using water and methanol (HPLC grade,J.T. Baker, Phillipsburgh, N.J.), and then dried at 80° C. under vacuumfor 16 h. Specific hydrothermal conditions (mL of TRIS solution/gram ofhybrid silica particle, concentration and pH of initial TRIS solution,reaction temperature) used to prepare these products are listed in Table4. The specific surface areas (SSA), specific pore volumes (SPV) and theaverage pore diameters (APD) of these materials are measured using themulti-point N₂ sorption method and are listed in Table 5. The specificsurface area was calculated using the BET method, the specific porevolume was the single point value determined for P/P₀>0.98, and theaverage pore diameter was calculated from the desorption leg of theisotherm using the BJH method. We also determined the micropore surfacearea (MPA), which we defined as the surface area in pores with diametersless than or equal to 34 Å, determined from the adsorption leg of theisotherm using the BJH method.

Methacryloxypropyl hybrid materials (e.g., 3q, 3r, 3s) were convertedinto 3-hydroxypropyl hybrid materials via hydrolysis of the ester bondduring hydrothermal treatment. Conversion of the ester into the alcoholgroup was observed by a decrease in the % C of the particles before vs.after treatment. ¹³C CPMAS NMR spectra of the hydrothermally treatedparticles detect 3-hydroxypropyl groups only, however, FTIR spectra ofthe particles indicate the existence of a carbonyl containing group asevidenced by a weak band at 1695 cm⁻¹. Higher concentrations of TRISsolution were required to modify the pore structure of these particlesbecause a portion of the base was sequestered as the methacrylic acidsalt. The composition of methacryloxypropyl particles post hydrothermaltreatment was relabeled to 3-hydroxypropyl. All post hydrothermalcompositions were confirmed using % CHN, FTIR, ¹³C and ²⁹Si CPMAS NMRspectroscopy.

TABLE 4 TRIS Conditions Prehydrothermal Composition of Amount Conc.Temp. Product Precursor Hybrid Materials (mL/g) (Molarity) pH (° C.) 3a2a SiO₂/(CH₃SiO_(1.5))_(0.2) 10 0.10 8.0 143 3b 2bSiO₂/(CH₃SiO_(1.5))_(0.2) 10 0.10 8.1 143 3c 2cSiO₂/(CH₃SiO_(1.5))_(0.2) 10 0.10 8.4 155 3d 2dSiO₂/(CH₃SiO_(1.5))_(0.35) 10 0.10 8.0 143 3e 2eSiO₂/(CH₃SiO_(1.5))_(0.5) 10 0.10 8.3 143 3f1 2f1SiO₂/(CH₃SiO_(1.5))_(0.5) 10 0.10 8.3 143 3f2 2f2SiO₂/(CH₃SiO_(1.5))_(0.5) 10 0.10 8.75 148 3f3 2f3SiO₂/(CH₃SiO_(1.5))_(0.5) 10 0.10 9.0 163 3g 2gSiO₂/(C₂H₃SiO_(1.5))_(0.25) 10 0.10 8.3 143 3i 2iSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.037) 5 0.10 10.2 165 3j 2jSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.125) 5 0.10 10.0 165 3k 2kSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) 5 0.30 10.0 165 3l 2lSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.5) 5 0.30 10.2 165 3m 2mSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.5) 5 0.30 10.2 165 3n 2nSiO₂/[C₂H₄(SiO_(1.5))₂]_(1.0) 5 0.30 10.2 165 3o 2oSiO₂/(H₂C═CHSiO_(1.5))_(0.25) 5 0.10 8.5 155 3p1 2pSiO₂/(H₂C═CHSiO_(1.5))_(0.5) 5 0.10 8.5 155 3p2 2pSiO₂/(H₂C═CHSiO_(1.5))_(0.5) 5 0.10 10.2 155 3q 2qSiO₂/[H₂C═C(CH₃)CO₂C₃H₆SiO_(1.5)]_(0.10) 5 0.75 10.7 155 3r 2rSiO₂/[H₂C═C(CH₃)CO₂C₃H₆SiO_(1.5)]_(0.125) 5 0.75 10.7 155 3t 2tSiO₂/(H₂C═CHC₆H₄C₂H₄SiO_(1.5))_(0.033) 5 0.10 9.6 155 3u 2uSiO₂/(H₂C═CHC₆H₄C₂H₄SiO_(1.5))_(0.10) 5 0.75 10.7 155

TABLE 5 N₂ Sorption Data Prod- Post-hydrothermal Composition SSA SPV APDMPA uct of Hybrid Materials (m²/g) (cc/g) (Å) (m²/g) 3aSiO₂/(CH₃SiO_(1.5))_(0.2) 130 0.41 103 72 3b SiO₂/(CH₃SiO_(1.5))_(0.2)151 0.71 159 14 3c SiO₂/(CH₃SiO_(1.5))_(0.2) 135 0.67 173 15 3dSiO₂/(CH₃SiO_(1.5))_(0.35) 160 0.72 139 14 3e SiO₂/(CH₃SiO_(1.5))_(0.5)225 0.90 123 21 3f1 SiO₂/(CH₃SiO_(1.5))_(0.5) 188 0.70 125 15 3f2SiO₂/(CH₃SiO_(1.5))_(0.5) 155 0.69 148 15 3f3 SiO₂/(CH₃SiO_(1.5))_(0.5)125 0.62 168 13 3g SiO₂/(C₂H₅SiO_(1.5))_(0.25) 267 0.94 139 53 3iSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.037) 162 0.52 122 28 3jSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.125) 127 0.81 238 31 3kSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) 162 0.52 122 28 3lSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.5) 122 0.48 133 23 3mSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.5) 155 0.45 101 34 3nSiO₂/[C₂H₄(SiO_(1.5))₂]_(1.0) 150 0.45 107 32 3oSiO₂/(H₂C═CHSiO_(1.5))_(0.25) 143 0.73 194 26 3p1SiO₂/(H₂C═CHSiO_(1.5))_(0.5) 219 0.65 141 101 3p2SiO₂/(H₂C═CHSiO_(1.5))_(0.5) 165 0.54 155 94 3qSiO₂/[HOC₃H₆SiO_(1.5)]_(0.10) 324 1.04 113 23 3rSiO₂/[HOC₃H₆SiO_(1.5)]_(0.125) 353 0.76 79 50 3t SiO₂/ 153 0.62 153 31(H₂C═CHC₆H₄C₂H₄SiO_(1.5))_(0.033) 3u SiO₂/ 193 0.55 102 58(H₂C═CHC₆H₄C₂H₄SiO_(1.5))_(0.10)

Example 5

The particles of hybrid silica prepared according to Example 4 wereseparated by particle size into ˜3, ˜5, and ˜7 μm fractions. Theparticles were then dispersed in a 1 molar hydrochloric acid solution(Aldrich Chemical) for 20 h at 98° C. After the acid treatment wascompleted, the particles were washed with water to a neutral pH,followed by acetone (HPLC grade, J.T. Baker, Phillipsburgh, N.J.). Theparticles were then dried at 80° C. under vacuum for 16 h.

Example 6

Vinyl hybrid silica particles (product 3p1 of Example 5) were sized andacid washed according to Example 5. A 20 g amount of the 5 μm vinylhybrid particles were added onto an 80 mm OD watch glass and placedinside a 90×170 mm (H×OD) crystallizing dish. Fuming bromine, 5 mL(Aldrich Chemical), was then added around the outside diameter of thewatch glass, and the crystallization dish was covered with an inverted100×190 mm (H×OD) crystallization dish. The bromination reaction wasperformed at ambient temperature for 18 h. Excess bromine wassubsequently removed, and the material was washed exhaustively withmethylene chloride (HPLC grade, J.T. Baker), water, and again withmethylene chloride. The brominated particles were then dried at 80° C.under vacuum for 16 h. Incorporation of 18.6% bromine was measured bycombustion-titration analysis (Galbraith Laboratories, Knoxyille,Tenn.), and 20% of the vinyl groups were converted into thedibromoethane analog as determined by ¹³C CPMAS NMR spectroscopy.

Example 7

Vinyl hybrid silica particles (product 3p1 of Example 5) were sized andacid washed according to Example 5. A 50 g amount of the 5 μm vinylhybrid particles was combined with 15.0 g p-toluenesulfonhydrazide(Aldrich Chemical), 14.3 g tripropylamine (Aldrich Chemical), and 300 mLo-xylene (Aldrich Chemical) in a 500 mL three-neck round-bottom flask.The reaction mixture was heated to 140° C. for 6 h. and was then cooledto room temperature (30° C.). The flask was recharged with the sameamount of p-toluenesulfonhydrazide and tripropylamine, and the reactionmixture was reheated to 140° C. for another 16 h. The particles werethen washed exhaustively with toluene, acetone, acetone/water (50/50,v/v), and acetone (all solvents HPLC grade, J.T. Baker). The washedparticles were then dried at 80° C. under vacuum for 16 h. The driedparticles were reacted an additional 7 successive times, as describedabove, to afford a 1/20 ratio of unreacted vinyl groups to hydrogenatedvinyl groups (i.e., ethyl). The vinyl content was found to decrease witheach successive reaction as measured by ¹³C CPMAS NMR spectroscopy.

Example 8

Vinyl hybrid silica particles (product 3p1 of Example 5) were sized andacid washed according to Example 5. A 10 g amount of the 5 μm vinylhybrid particles was combined with 62 g of 4,4′-azobis(4-cyanovalericacid) (Aldrich Chemical) in 125 mL of a methanol/water (50/50, v/v)solution. The suspension was deoxygenated by bubbling argon gas throughit for 1 h, after which an argon blanket was maintained over thesuspension. The suspension was then heated to 70° C. for 20 h andsubsequently cooled to room temperature. The mixture was transferred toa filter apparatus and washed exhaustively with toluene, acetone/water(50/50, v/v), and acetone (all solvents HPLC grade, J.T. Baker). Thewashed particles were then dried at 80° C. under vacuum for 16 h.Coupling of 4-cyanovaleric acid to the vinyl group of the skeletalstructure through a covalent organic bond was established by an 18%increase in particle carbon content, and an ion-exchange capacity of0.18 meq/g assigned to the carboxylic group.

Example 9

Vinyl hybrid silica particles (product 3p1 of Example 5) were sized andacid washed according to Example 5. A 10 g amount of the 5 μm vinylhybrid particles was combined with 62 g of2,2′-azobis(2-methylpropionamidine) dihydrochloride (Aldrich Chemical)in 125 mL of a methanol/water (50/50, v/v) solution. The suspension wasdeoxygenated by bubbling argon gas through it for 1 h, after which anargon blanket was maintained over the suspension. The suspension washeated to 50° C. for 20 h and subsequently cooled to room temperature.The mixture was transferred to a filter apparatus and washedexhaustively with toluene, acetone/water (50/50, v/v), and acetone (allsolvents HPLC grade, J.T. Baker). The washed particles were then driedat 80° C. under vacuum for 16 h. Coupling of (2-methylpropionamidine)hydrochloride to the vinyl group of the skeletal structure through acovalent organic bond was established by a 10% increase in particlecarbon content, and an ion-exchange capacity of 0.15 meq/g, assigned tothe amidine hydrochloride group. Furthermore, ¹³C CPMAS NMR spectroscopyof the particles showed resonances assigned to the2-methylpropionamidine group.

Example 10

Vinyl hybrid silica particles (product 3p1 of Example 5) were sized andacid washed according to Example 5. A 2 g amount of the 7 μm vinylhybrid particles was combined with 2.1 g of N-octadecylacrylamide(Aldrich Chemical) in 20 mL of toluene (J.T. Baker). The suspension wasdeoxygenated by bubbling argon gas through it for 1 h, after which anargon blanket was maintained over the suspension. While maintaining anargon blanket, 0.4 g of VAZO 88 was added to the reaction, and thereaction mixture was heated to 70° C. for 17 h. The flask was thencooled to room temperature, and the particles were transferred to afilter apparatus. The filtered particles were washed exhaustively withtetrahydrofuran, toluene, acetone, acetone/water (50/50, v/v), andacetone (all solvents HPLC grade, J.T. Baker). The washed particles werethen dried at 80° C. under vacuum for 16 h. Radical initiated couplingof octadecylacrylamide groups with vinyl groups of the skeletalstructure through a covalent organic bond was established by a 29%increase in particle carbon content, which converts to a surfaceconcentration of 1.02 μmol/m². Furthermore, ¹³C CPMAS NMR and FTIRspectroscopy of the particles showed resonances consistent withoctadecylacrylamide addition to the vinyl groups.

Example 11

Vinyl hybrid silica particles (product 3p1 of Example 5) were sized andacid washed according to Example 5. A 3 g amount of the 7 μm vinylhybrid particles was combined with 0.9 g dicyclopentadiene (AldrichChemical) in 25 mL of toluene (J.T. Baker). The suspension was heated toreflux (111° C.) for 16 h and then cooled to room temperature. Theparticles were transferred to a filter apparatus and washed exhaustivelywith toluene and acetone (both HPLC grade, J.T. Baker). The washedparticles were then dried at 80° C. under vacuum for 16 h. Diels-Aldercycloaddition of cyclopentadiene with the vinyl groups through acovalent organic bond was established by a 14% increase in particlecarbon content that is analogous to a surface concentration of 1.36μmol/m². Furthermore, ¹³C CPMAS NMR and FTIR spectroscopy of theparticles showed resonances consistent with diene addition.

Example 12

Propanol hybrid silica particles (product 3q of Example 5) were sizedand acid washed according to Example 5. A 3 g amount of the dried 6 μmpropanol hybrid particles and 4.9 g of octylisocyanate (AldrichChemical) were combined with 75 mL of dry toluene (J.T. Baker) under anargon blanket. The suspension was heated to reflux (111° C.) for 4 h andthen cooled to 60° C. The particles were transferred to a filterapparatus and washed exhaustively with toluene heated to 80° C. and thenroom temperature acetone (both HPLC grade, J.T. Baker). The washedparticles were then dried at 80° C. under vacuum for 16 h. Reaction ofthe octyl isocyanate molecule with the hybrid particle's hydroxyl groupto form a carbamate group and thereby connect the octyl chain to theparticle's skeletal structure through a covalent organic bond wasestablished by a 94% increase in particle carbon content that isanalogous to a surface concentration of 1.59 μmol/m² of O-propylsilylN-octyl carbamate group. Furthermore, ¹³C CPMAS NMR spectroscopy of theparticles showed resonances consistent with addition product, where 40%of the propanol groups were converted to carbamate groups, and theremaining propanol groups remained unreacted.

Example 13

A 3 g amount of the dried 6 μm propanol hybrid particles, as describedin Example 12, and 6.7 g of dodecyl isocyanate (Aldrich Chemical) werecombined with 75 mL of dry toluene (J.T. Baker) and reacted in the sameway as described in Example 12. Addition of the dodecyl isocyanatemolecule to the hybrid particle's hydroxyl group to form a carbamategroup and thereby connect the dodecyl chain to the particle's skeletalstructure through a covalent organic bond was established by thereaction procedure and a 119% increase in particle carbon content thatis analogous to a surface loading of 1.41 μmol/m² of O-propylsilylN-dodecyl carbamate group. Furthermore, ¹³C CPMAS NMR spectroscopy ofthe particles showed resonances consistent with addition product, where40% of the propanol groups were converted to carbamate groups, and theremaining propanol groups remained unreacted.

Example 14

Propanol hybrid silica particles (product 3q of Example 5) were sizedand acid washed according to Example 5. A 3 g amount of the dried 6 μmpropanol hybrid particles, 0.47 g of p-toluenesulfonic acid (AldrichChemical), and 10.0 g of lauric acid (Sigma Chemical, St. Louis, Mo.)were combined with 100 mL of dry xylene (J.T. Baker) under an argonblanket. The suspension was heated to reflux (145° C.) for 16 h and thencooled to 30° C. The particles were then transferred to a filterapparatus and washed exhaustively with toluene, acetone, acetone/water(50/50, v/v), and acetone again (all solvents HPLC grade, J.T. Baker).The washed particles were then dried at 80° C. under vacuum for 16 h.Reaction of the lauric acid molecule with the hybrid particle's hydroxylgroup to form a carboxylic acid ester bond and thereby connect then-C₁₁H₂₃ alkyl chain to the particle's skeletal structure through acovalent organic bond was established by the reaction procedure and a157% increase in particle carbon content, which converts to a surfaceconcentration of 2.06 μmol/m² of n-C₁₁H₂₃ alkyl groups. Furthermore, ¹³CCPMAS NMR spectroscopy of the particles showed resonances consistentwith ester product, where 30% of the propanol groups were converted toester groups, and the remaining propanol groups remained unreacted.

Example 15

Propanol hybrid silica particles (product 3q of Example 5) were sizedand acid washed according to Example 5. A 3 g amount of the dried 6 μmpropanol hybrid particles and 3.3 mL of dried triethylamine (AldrichChemical) were combined with 150 mL of dry dichloromethane (HPLC grade,J.T. Baker) under an argon blanket and chilled to 5° C. Maintaining atemperature of 5° C., 1.95 mL of methacryloyl chloride (AldrichChemical) was added dropwise to the suspension. Three additionalaliquots of triethylamine and methacryloyl chloride were added for acombined total of 13.2 mL triethylamine and 7.8 mL methacryloylchloride. The suspension was allowed to warm to room temperature and wasstirred an additional 16 h. The particles were transferred to a filterapparatus and washed exhaustively with dichloromethane, acetone, water,and again with acetone (all solvents HPLC grade, J.T. Baker). The washedparticles were then dried at 80° C. under vacuum for 16 h. Reaction ofthe methacryloyl chloride molecule with the hybrid particle's hydroxylgroup to form a carboxylic acid ester bond and thereby connect themethacrylate's vinyl group to the particle's skeletal structure througha covalent organic bond was established by a 63% increase in particlecarbon content that is analogous to a surface concentration of 2.30μmol/m² of methacrylate groups. Furthermore, ¹³C CPMAS NMR spectroscopyof the particles showed resonances consistent with ester product, where60% of the propanol groups were converted to ester groups, and theremaining propanol groups remained unreacted.

Example 16

A 0.5 g amount of the dried styrylethyl hybrid particles (product 3t ofExample 5) was brominated in the manner described in Example 6. Greaterthan 99% of the vinyl groups were converted into the dibromoethaneanalog as determined by ¹³C CPMAS NMR spectroscopy.

Example 17

Styrylethyl hybrid silica particles (product 3u of Example 5) were sizedaccording to Example 5. A 0.5 g amount of the dried 8 μm styrylethylhybrid particles was brominated in the manner described in Example 6.Greater than 99% of the vinyl groups were converted into thedibromoethane analog as determined by ¹³C CPMAS NMR spectroscopy.

Example 18

A 2.0 g amount of the dried styrylethyl hybrid particles (product 3t ofExample 5) was suspended in 20 mL of toluene (J.T. Baker) and refluxedfor 2 h under an argon atmosphere to deoxygenate and removed adsorbedwater via azeotrope. After cooling to room temperature under dry argon,0.6 g of 1,1′-azobis(cyclohexanecarbonitrile) (Aldrich Chemical) wasadded. The suspension was stirred and heated to 80° C. for 17 h thenheated to 100° C. for 2.5 h. After cooling, the particles were recoveredby filtration, and exhaustively washed with toluene, dichloromethane andacetone. The washed particles were then dried at 80° C. under vacuum for16 h. Reaction of the cyclohexanecarbonitrile molecule with the hybridparticle's vinyl group, thereby connecting the reagent to the particle'sskeletal structure through a covalent organic bond was established by a23% increase in particle carbon content that is analogous to a surfaceconcentration of 1.09 μmol/m² of cyclohexanecarbonitrile groups. Greaterthan 99% of the vinyl groups were polymerized as determined by ¹³C CPMASNMR spectroscopy.

Example 19

Styrylethyl hybrid silica particles (product 3u of Example 5) were sizedaccording to Example 5. A 2.0 g amount of the dried 8 μm styrylethylhybrid particles was reacted with 0.9 g of1,1′-azobis(cyclohexanecarbonitrile) in the manner described above forExample 18. Reaction of the cyclohexanecarbonitrile molecule with thehybrid particle's vinyl group, thereby connecting the reagent to theparticle's skeletal structure through a covalent organic bond wasestablished by a 9.7% increase in particle carbon content, whichconverts to a surface concentration of 1.07 μmol/m² ofcyclohexanecarbonitrile groups. Greater than 99% of the vinyl groupswere polymerized as determined by ¹³C CPMAS NMR spectroscopy

Example 20

A 2.0 g amount of the dried styrylethyl hybrid particles (product 3t ofExample 5) was combined with 0.29 g of1,1′-azobis(cyclohexanecarbonitrile) (Aldrich Chemical) and 25 mL ofdichloromethane (J.T. Baker) in a 25 mL round-bottom flask. Afterstirring the suspension until the radical initiator was dissolved, thedichloromethane was removed from the suspension by rotary-evaporation.The initiator coated particles were dried under high vacuum (0.1 mm Hg)for 18 h. In a similar sized flask, 10 mL of styrene (Aldrich Chemical)was added and degassed via high vacuum. Under a closed, reduced pressuresystem, styrene vapor was allowed to equilibrate between the two flasksfor 1.5 h, thereby adsorbing onto the styrylethyl hybrid particles. Thecoated, styrylethyl hybrid particles were then vented to argon andheated to 80° C. for 20 h. After cooling, the particles were recoveredby filtration and exhaustively washed with toluene, dichloromethane andacetone. The washed particles were then dried at 80° C. under vacuum for16 h. Greater than 99% of the vinyl groups were copolymerized with theadsorbed styrene as determined by ¹³C CPMAS NMR spectroscopy. Reactionof the cyclohexanecarbonitrile and styrene molecules with the hybridparticle's vinyl group thereby connecting the reagents to the particle'sskeletal structure through a covalent organic bond was established by a16.3% increase in particle carbon content.

Example 21

Styrylethyl hybrid silica particles (product 3u of Example 5) were sizedaccording to Example 5. A 2.0 g amount of the dried 8 μm styrylethylhybrid particles was reacted with 0.25 g of1,1′-azobis(cyclohexanecarbonitrile) in the manner described above forExample 20. Greater than 99% of the vinyl groups were copolymerized withthe adsorbed styrene as determined by ¹³C CPMAS NMR spectroscopy.Reaction of the cyclohexanecarbonitrile and styrene molecules with thehybrid particle's vinyl group, thereby connecting the reagents to theparticle's skeletal structure through a covalent organic bond wasestablished by a 42% increase in particle carbon content.

Example 22

Styrylethyl hybrid silica particles (product 3u of Example 5) were sizedaccording to Example 5. A 2.0 g amount of the dried 8 μm styrylethylhybrid particles was reacted with 0.20 g of1,1′-azobis(cyclohexanecarbonitrile) in the manner described above forExample 20, with the exception that divinylbenzene (Aldrich Chemical)was used as the adsorbed monomer. Greater than 99% of the vinyl groupswere copolymerized with the adsorbed divinylbenzene as determined by ¹³CCPMAS NMR spectroscopy. Reaction of the cyclohexanecarbonitrile anddivinylbenzene molecules with the hybrid particle's vinyl group, therebyconnecting the reagents to the particle's skeletal structure through acovalent organic bond was established by a 37% increase in particlecarbon content.

Example 23

The surfaces of the hybrid silica particles were modified with a varietyof chlorotrialkylsilanes as follows: 1×10⁻⁵ moles of silane per squaremeter of particle surface area and 1.2 equivalents (per mole silane) ofa base activator such as 4-(dimethylamino)pyridine (Aldrich Chemical),imidazole (Aldrich Chemical), or pyridine (J.T. Baker) were added to amixture of 10 g of hybrid silica in 50 mL of toluene (J.T. Baker), andthe resultant mixture was refluxed for 2-4 h. The modified hybrid silicaparticles were filtered and washed successively with water, toluene, 1:1v/v acetone/water, and acetone (all solvents from J.T. Baker), and thendried at 80° C. under reduced pressure for 16 h. The surfaceconcentration (μmol/m²) of trialkylsilyl groups was determined by thedifference in particle % C before and after the surface modification asmeasured by elemental analysis.

A secondary surface modification or end capping reaction was performedusing a second silane, chlorotrimethylsilane (Aldrich Chemical),following the above procedure with respect to reagent amounts andreaction conditions. Table 6 lists the unmodified hybrid particlecomposition, the chemical formula of the first silane, the chemicalformula of the second or end capping silane, the surface concentrationof the first silane bonded phase, and total % C for selected finalmodified particles. Silanes and their sources were as follows:chlorodimethyloctadecylsilane and chlorotrimethylsilane (both fromAldrich Chemical); 3-(chlorodimethylsilyl)propyl N-octadecylcarbamate,3-(chlorodimethylsilyl)propyl N-dodecylcarbamate, and3-(chlorodimethylsilyl)propyl N-benzylcarbamate (all prepared asdescribed in Neue, Niederländer, and Petersen in U.S. Pat. No.5,374,755); [3-(pentafluorophenyl)-propyl]dimethylchlorosilane,octyldiisopropylchlorosilane, and triacontyldimethylchlorosilane (allfrom Gelest, Inc.).

TABLE 6 Composition of Secondary Silane Surface % C Final HybridMaterial Chemical Concentration Modified Product Prior to ModificationPrimary Silane Chemical Formula Formula (μmol/m²) Particle 24aSiO₂/(CH₃SiO_(1.5))_(0.2) CH₃(CH₂)₁₇Si(CH₃)₂Cl ClSi(CH₃)₃ 2.73 11.06 24bSiO₂/(CH₃SiO_(1.5))_(0.35) CH₃(CH₂)₁₇Si(CH₃)₂Cl ClSi(CH₃)₃ 2.50 14.8024c SiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₁₇Si(CH₃)₂Cl ClSi(CH₃)₃ 2.18 15.0224d SiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₁₇Si(CH₃)₂Cl ClSi(CH₃)₃ 2.23 17.2124e SiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₁₇NHC(O)O(CH₂)₃Si(CH₃)₂ClClSi(CH₃)₃ 1.80 14.84 24f SiO₂/(CH₃SiO_(1.5))_(0.5)CH₃(CH₂)₁₁NHC(O)O(CH₂)₃Si(CH₃)₂Cl ClSi(CH₃)₃ 2.34 14.74 24gSiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₇NHC(O)O(CH₂)₃Si(CH₃)₂Cl ClSi(CH₃)₃2.42 13.46 24h SiO₂/(CH₃SiO_(1.5))_(0.5)C₆H₅(CH₂)NHC(O)O(CH₂)₃Si(CH₃)₂Cl ClSi(CH₃)₃ 2.49 13.02 24iSiO₂/(CH₃SiO_(1.5))_(0.5) C₆F₅(CH₂)₃Si(CH₃)₂Cl ClSi(CH₃)₃ 2.27 11.66 24jSiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₇Si[CH(CH₃)₂]₂Cl ClSi(CH₃)₃ 1.23 10.7624k SiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₂₉Si(CH₃)₂Cl ClSi(CH₃)₃ 1.94 18.4824l SiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) CH₃(CH₂)₁₁NHC(O)O(CH₂)₃Si(CH₃)₂ClClSi(CH₃)₃ 2.55 15.28 24m SiO₂/[HOC₃H₆SiO_(1.5)]_(0.10)CH₃(CH₂)₇Si[CH(CH₃)₂]₂Cl — 1.74 13.89 24n SiO₂/[RSiO_(1.5)]_(0.10) whereClSi(CH₃)₃ — 2.44 12.95 R = 60% HOC₃H₆ and 40% CH₃(CH₂)₇NHC(O)OC₃H₆ 24oSiO₂/[RSiO_(1.5)]_(0.10) where ClSi(CH₃)₃ — 3.10 14.50 R = 60% HOC₃H₆and 40% CH₃(CH₂)₁₁NHC(O)OC₃H₆

Example 24

The surfaces of the hybrid silica particles were modified with a varietyof dialkyldichlorosilanes, alkyltrichlorosilanes, andalklytrialkoxysilanes as follows: 1×10⁻⁵ moles of silane per squaremeter of particle surface area and 1.2 equivalents (per mole silane) ofa base activator such as 4-(dimethylamino)pyridine (Aldrich Chemical),imidazole (Aldrich Chemical), or pyridine (J.T. Baker) were added to amixture of 10 g of hybrid silica in 50 mL of toluene (J.T. Baker) andthe resultant mixture was refluxed for 2-4 h. The modified hybrid silicaparticles were filtered and washed successively with toluene, 1:1 v/vacetone/water, and acetone (all solvents from J.T. Baker). The washedparticles were then heated in a 4.5:1 v/v solution of acetone/0.12 Mammonium acetate for 2.0-3.0 hours at 60° C. The particles weresubsequently cooled, filtered, and washed successively with 1:1 v/vacetone/water, and acetone, and then dried at 80° C. under reducedpressure for 16 h. The surface concentration (μmol/m²) of dialkylsilyland alkylsilyl groups was determined by the difference in particle % Cbefore and after the surface modification as measured by elementalanalysis.

A secondary surface modification or end capping reaction was run using asecond silane, including chlorotrimethylsilane, chlorotriethylsilane,and tert-butyldimethylchlorosilane (all from Aldrich Chemical),following the above procedure with respect to reagent amounts andreaction conditions. Table 7 lists the unmodified hybrid particlecomposition, the chemical formula of the first silane, the chemicalformula of the second or end capping silane, the surface concentrationof the first silane bonded phase, and total % C for selected finalmodified particles. Silanes and their sources were as follows:octadecyltrichlorosilane (Aldrich Chemical);octadecylmethyldichlorosilane, (3-phenylpropyl)trichlorosilane,(3-phenylpropyl)methyldichlorosilane,(4-phenylbutyl)methyldichlorosilane, phenethyltrichlorosilane,[3-(pentafluorophenyl)propyl]trichlorosilane, triacontyltrichlorosilane(all from Silar Laboratories, Scotia, N.Y.);(2-phenylpropyl)methyldichlorosilane (Gelest Inc.);1H,1H,2H,2H-perfluorooctyltriethoxysilane (Sivento, Piscataway, N.J.);phenyltrichlorosilane, 3-cyanopropyltrichlorosilane (Hüls, Piscataway,N.J.).

TABLE 7 Composition of Surface % C Final Hybrid Material PrimarySecondary Silane Concentration Modified Product Prior to ModificationSilane Chemical Formula Chemical Formula (μmol/m²) Particle 25aSiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₁₇Si(CH₃)Cl₂ ClSi(CH₃)₃ 2.23 15.31 25bSiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅(CH₂)₃Si(CH₃)Cl₂ ClSi(CH₃)₃ 2.31 12.25 25cSiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅(CH₂)₃Si(CH₃)Cl₂ ClSi(CH₂CH₃)₃ 2.31 12.3925d SiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅(CH₂)₃Si(CH₃)Cl₂ Cl(CH₃)₂SiC(CH₃)₃2.31 12.07 25e SiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅(CH₃)CHCH₂Si(CH₃)Cl₂ClSi(CH₃)₃ 2.11 11.76 25f SiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅(CH₂)₄Si(CH₃)Cl₂ClSi(CH₃)₃ 2.37 12.76 25g SiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₂₉SiCl₃ClSi(CH₃)₃ 2.30 19.84 25h SiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₁₇SiCl₃ClSi(CH₃)₃ 2.13 15.43 25i SiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₁₇SiCl₃ClSi(CH₂CH₃)₃ 2.13 15.75 25j SiO₂/(CH₃SiO_(1.5))_(0.5) CH₃(CH₂)₁₇SiCl₃Cl(CH₃)₂SiC(CH₃)₃ 2.13 15.33 25k SiO₂/(CH₃SiO_(1.5))_(0.5)CH₃(CH₂)₇SiCl₃ ClSi(CH₃)₃ 2.23 11.70 25l SiO₂/(CH₃SiO_(1.5))_(0.5)CF₃(CF₂)₅(CH₂)₂Si(OCH₂CH₃)₃ ClSi(CH₃)₃ 1.46 9.90 25mSiO₂/(CH₃SiO_(1.5))_(0.5) C₆F₅(CH₂)₃SiCl₃ ClSi(CH₃)₃ 2.13 11.67 25nSiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅(CH₂)₂SiCl₃ ClSi(CH₃)₃ 2.42 12.02 25oSiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅(CH₂)₂SiCl₃ ClSi(CH₂CH₃)₃ 2.35 12.09 25pSiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅(CH₂)₂SiCl₃ Cl(CH₃)₂SiC(CH₃)₃ 2.42 11.7225q SiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅(CH₂)₄SiCl₃ ClSi(CH₃)₃ 2.20 12.57 25rSiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅SiCl₃ ClSi(CH₃)₃ 2.09 10.74 25sSiO₂/(CH₃SiO_(1.5))_(0.5) C₆H₅SiCl₃ Cl(CH₃)₂SiC(CH₃)₃ 2.09 10.88 25tSiO₂/(CH₃SiO_(1.5))_(0.5) NC(CH₂)₃SiCl₃ — 2.31 — 25uSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) CH₃(CH₂)₁₇SiCl₃ ClSi(CH₃)₃ 2.62 15.74 25vSiO₂/(H₂C═CHSiO_(1.5))_(0.5) CH₃(CH₂)₁₇SiCl₃ ClSi(CH₃)₃ 1.28 18.26 25wSiO₂/(RSiO_(1.5))_(0.5) where CH₃(CH₂)₁₇SiCl₃ ClSi(CH₃)₃ 1.73 14.31 R =20% BrCH₂CHBr and 80% H₂C═CH 25x SiO₂/(RSiO_(1.5))_(0.5) whereCH₃(CH₂)₁₇SiCl₃ ClSi(CH₃)₃ 1.38 17.14 R = 95% CH₃CH₂ and 5% H₂C═CH 25ySiO₂/(RSiO_(1.5))_(0.5) where CH₃(CH₂)₁₇SiCl₃ ClSi(CH₃)₃ 0.86 18.29 R =3.4% HO₂CCH₂CH₂C(CH₃)(CN)—CH₂CH₂ and 96.6% H₂C═CH 25zSiO₂/(RSiO_(1.5))_(0.5) where CH₃(CH₂)₁₇SiCl₃ ClSi(CH₃)₃ 1.23 18.85 R =3.4% HCl•H₂N(HN═)C(CH₃)₂—CH₂CH₂ and 96.6% H₂C═CH 25aaSiO₂/[HOC₃H₆SiO_(1.5)]_(0.10) CH₃(CH₂)₂₉SiCl₃ ClSi(CH₃)₃ 2.16 19.03 25bbSiO₂/[HOC₃H₆SiO_(1.5)]_(0.10) CH₃(CH₂)₁₇SiCl₃ ClSi(CH₃)₃ 2.30 25.47 25ccSiO₂/[HOC₃H₆SiO_(1.5)]_(0.10) C₆F₅(CH₂)₃SiCl₃ ClSi(CH₃)₃ 1.92 13.01

Example 25

Selected examples of surface derivatized hybrid silicas from Example 23were used for the separation of a mixture of neutral, polar and basiccompounds listed in Table 8. The 3.9×150 mm chromatographic columns werepacked using a slurry packing technique. The HPLC system consisted of anAlliance 2690 XE separations module, a model 996 photodiode arraydetector, a Millennium³² v.2.15.01 data management system (all fromWaters Corporation, Milford, Mass.), and a NESLAB RTE-111 circulatingwater bath for column temperature control (NESLAB Instruments, Inc.,Portsmouth, N.H.). Mobile phase conditions were: 20 mM KH₂PO₄/K₂HPO₄, pH7.0/methanol (35:65 v/v); flow rate: 1.0 mL/min; temperature: 23.4° C.;detection: 254 nm.

TABLE 8 Product Product 19b in Product 19c in 19d in Table 6 Table 6Table 6 k of Acenaphthene 10.02 11.35 13.40 Relative Retention (r)Propranolol/Acenaphthene 0.157 0.149 0.139 Butyl paraben/Acenaphthene0.226 0.216 0.223 Dipropyl Phthalate/Acenaphthene 0.411 0.405 0.403Naphthalene/Acenaphthene 0.437 0.436 0.437 Amitriptyline/Acenaphthene1.483 1.525 1.395It can be seen that the packing materials based on the hybrid materialsprovide ample retention and resolution in the separation of neutral,polar, and basic compounds. (Relative retention is the (k of theanalyte) divided by the (k of acenaphthene). Therefore values less thanone, indicate less retention than acenaphthene, and values greater thanone, indicate more retention than acenaphthene. Relative retention is awell known parameter in the field of HPLC.)

Example 26

Selected examples of surface derivatized hybrid materials from Examples23 and 24 as well as similarly derivatized commercial columns based onsilica which have similar alkyl silyl groups were evaluated for basiccompound USP peak tailing factors using the mobile phase and testconditions of Example 25. The results are shown in Table 9.

TABLE 9 USP Tailing Factors Column Propranolol Amitriptyline CommercialColumn A 1.6 3.6 (C₃₀ Type) Example 23j (C₃₀ Type) 1.3 2.3 CommercialColumn C 4.2 7.0 (C₁₈ Type) Commercial Column D 1.3 1.8 (C₁₈ Type)Commercial Column E 1.0 1.7 (C₁₈ Type) Commercial Column F 1.3 1.5 (C₁₈Type) Example 23b (C₁₈ Type) 1.1 1.0 Example 23c (C₁₈ Type) 1.0 1.4Example 23d (C₁₈ Type) 1.0 1.4 Example 24a (C₁₈ Type) 1.0 1.3 Example24h (C₁₈ Type) 1.1 1.3 Example 24i (C₁₈ Type) 1.2 1.7 Example 24u (C₁₈Type) 1.1 2.0 Commercial Column I 1.3 1.3 (Embedded Polar Type) Example23f 1.1 1.2 (Embedded Polar Type) Example 23l 1.0 1.1 (Embedded PolarType) Commercial Column J 1.1 1.3 (C₈ Type) Commercial Column K 1.2 1.4(C₈ Type) Example 23k (C₈ Type) 1.1 1.3 Commercial Column L 1.8 3.9 (PhType) Commercial Column M 2.1 1.6 (Ph Type) Example 23h (Ph Type) 1.31.2 Example 24c (Ph Type) 1.2 1.4 Example 24e (Ph Type) 1.1 1.5 Example24f (Ph Type) 1.0 1.3 Commercial Column O 3.8 6.9 (C₆F₅ Type) CommercialColumn P 1.3 4.2 (C₆F₅ Type) Example 23i (C₆F₅ 1.2 1.4 Type) Example 24m(C₆F₅ 2.3 1.8 Type) Commercial Column Q 1.7 3.0 (CN type) Example 24t(CN Type) 1.2 1.4 It can be seen that the basic compound tailing factorson the packing materials based on the hybrid materials were generallylower than on the commercial silica-based materials (a lower valuecorresponds to reduced tailing).

Example 27

Selected examples of surface derivatized hybrid silicas from Examples 23and 24 as well as similarly derivatized commercial columns based onsilica gel which have similar alkyl silyl groups were evaluated forstability in alkaline mobile phases using the following procedure.Columns were prepared by slurry packing the materials into 4.6×150 mmsteel columns, and the analysis conditions were as follows: 1) The platenumber, N, (5 sigma method) was measured for a test analyte,acenaphthene. Mobile phase conditions were acetonitrile-20 mMKH₂PO₄/K₂HPO₄ pH 7.00 (40:60, v/v) at a flow of 1.0 mL/min and a columntemperature of 50.0° C. 2) The column was purged with 50 mMtriethylamine pH 10.00 mobile phase and run for 15 mM in the 50 mMtriethylamine pH 10.00 mobile phase at a flow of 2.0 mL/min and a columntemperature of 50.0° C. 3) In 15 mM increments, the column was purgedwith 100% water (10 minutes at 2.0 mL/minute) and then purged with 100%methanol (10 minutes at 2.0 mL/minute). 4) The column was then purgedand equilibrated with the mobile phase of step 1 above, and N foracenaphthene was measured. 5) The process was then repeated starting atstep 2. Packed columns were kept in a 50° C. water bath throughout thetest. Column lifetime is defined as the time of exposure to the pH 10triethylamine solution when the efficiency of the column drops to 50% ofits initial value. The results are shown in Table 10.

TABLE 10 Column Lifetime (h) Commercial Column A (C₃₀ Type) 17 Example23j (C₃₀ Type) 57 Commercial Column C (C₁₈ Type) 18 Commercial Column D(C₁₈ Type) 17 Commercial Column E (C₁₈ Type) 28 Commercial Column F (C₁₈Type) 23 Commercial Column G (C₁₈ Type) 23 Example 23a (C₁₈ Type) 51Example 23c (C₁₈ Type) 48 Example 23d (C₁₈ Type) 50 Example 24a (C₁₈Type) 36 Example 24h (C₁₈ Type) 41 Example 24i (C₁₈ Type) 34 Example 24u(C₁₈ Type) >153 Example 24x (C₁₈ Type) 41 Commercial Column I (EmbeddedPolar Type) 29 Example 23f (Embedded Polar Type) 32 Example 23l(Embedded Polar Type) 303 Commercial Column J (C₈ Type) 18 CommercialColumn K (C₈ Type) 13 Example 23k (C₈ Type) 26 Commercial Column L (PhType) 20 Commercial Column M (Ph Type) 16 Example 23h (Ph Type) 29Example 24c (Ph Type) 25 Example 24e (Ph Type) 26 Example 24f (Ph Type)29 Commercial Column O (C₆F₅ Type) 14 Commercial Column P (C₆F₅ Type) 6Example 23i (C₆F₅ Type) 24 Example 24m (C₆F₅ Type) 18 Commercial ColumnQ (CN type) 5 Example 24t (CN Type) 9 It is evident that the lifetimesof the columns containing hybrid packing materials are greatly improvedover the commercial columns containing silica-based materials.

Example 28

A 4.6×50 mm chromatography column was packed with a mixture of 2.5 μmXTerra® MS C18 (Waters Corporation), or the product of Example 24 h andunbonded 1.8 μm spherical silica particles using a downward slurrytechnique. The column packing apparatus comprised a high-pressure liquidpacking pump (Model No: 10-500FS100 or equivalent, SC HydraulicEngineering Corp., Los Angeles, Calif.) and a slurry packing reservoir(55 mL). The assembled column was connected to a packing reservoir, anda slurry of the mixed stationary phase (6:1 volume ratio of XTerra MSC18 to unbonded silica particles) was suspended in a toluene:methylethyl ketone 85:15 (v/v) mixture, sonicated for 5 min, and then pouredinto the packing reservoir. The reservoir was closed and methanol wasthen pumped through the column, ultimately reaching a pressure of 6000PSI. After allowing sufficient time for bed consolidation, the pump wasturned off and the pressure was released.

The column was rinsed with 0.1 M NaOH, and then with acetone. The columnwas purged with N₂ gas for 1 hour, providing rapid drying. Physicallyadsorbed water was removed by heating the column at 120° C. for 4 hoursin a vacuum oven (F6000 or equivalent, Barnstead/Thermolyne Corporation,Dubuque, Iowa). The column was then purged with N₂ gas for 60 min andsealed. The sealed column was sintered in a furnace (VWR 1410 orequivalent, VWR Scientific Products, Boston, Mass.) for 12 hours at 300°C.

The resulting column containing the reversed-phase hybrid particles wasrinsed with acetone and then dried by purging with N₂ for 24 hours. Thisdrying step was added to minimize the wetting of the reversed-phasesurface. The column was washed with 10 mL 0.1 N NaOH aqueous solution,and then with 40 mL 0.01N NaOH aqueous solution at 50° C. Subsequently,the column was washed with water while gradually decreasing thetemperature to 20° C. The column was ultimately rinsed with acetonitrileat room temperature to produce a column containing a hybridinorganic/organic monolith material comprised of coalesced hybridinorganic/organic particles.

FIG. 1 indicates the pressure change before and after the sintering andwashing steps described above as a function of the amount of unbondedsilica used in the original mixture.

Example 29

Pluronic P-105, 0.7 g, (from BASF Corp., Mount Olive, N.J.) wasdissolved in 5 mL of an acetic acid solution selected from the followingconcentrations, respectively: 30 mM, 50 mM, 70 mM, and 110 mM. Theresulting solution was agitated at room temperature until all of thePluronic P-105 was dissolved and was then chilled in an ice-water bath.

Meanwhile, methyltrimethoxysilane, 5 mL, and tetramethoxysilane, 10 mL,(both from Gelest Inc., Tullytown, Pa.) were mixed at room temperaturein a separate, sealed flask. An aliquot of 2 mL of the mixed silanesolution was slowly added into the chilled acetic acid mixture,whereupon the silanes dissolved into the acetic acid solution after afew minutes. The resulting transparent solution was transferred into asealed polypropylene container (9.6 mm×10 cm) and kept at 45° C.undisturbed for 2 days. The solid white rod produced was subsequentlyimmersed into 100 mL 0.1 N aqueous ammonium hydroxide solution for 3days at 60° C. The monolith material was then washed with water for 2days, solvent-exchanged to methanol for 1 day, and then dried in air for5 hours. The monolith material was then dried under vacuum at 135° C.for 3 days, resulting in a white rod without any cracks.

The morphologies of the formed rods were observed by a scanning electronmicroscope. It was observed that a three-dimensional interconnectednetwork was formed within the rods and that the skeleton thicknessincreased as the acetic acid concentration increased. As listed in Table11, the monolith material obtained from 30 mM acetic acid solution had askeleton thickness less than 0.5 μm, while the monolith materialobtained from 110 mM acetic acid solution had a skeleton thicknessaround 5 μm.

Median pore diameter (MPD) and pore volume (PV) of thus formed rods weremeasured by Mercury Porosimetry. The specific surface areas (SSA),specific pore volumes (SPV) and the average pore size diameters (APD) ofthe mesopores were measured using the multi-point N₂ sorption method.Results are compiled in Table 11. The specific surface area wascalculated using the BET method, the specific pore volume was the singlepoint value determined for P/P₀>0.98, and the average pore diameter wascalculated from the desorption leg of the isotherm using the BJH method.

TABLE 11 Acetic Acid Skeleton Concentration Thickness MPD PV(1) MPDPV(2) SSA SPV APD Product (mM) (μm) (μm) (cc/g) (Å) (cc/g) (m²/g) (cc/g)(Å) 29a 30 <0.5 0.3 4.5 — — 850 1.98 92 29b 50 0.7 0.35 4.0 — — 841 1.9692 29c 70 2 2.2 3.12 265 1.62 682 1.81 102 29d 110 5 16.3 2.61 139 0.96939 1.33 57

Example 30

Triton X-100, 0.7 g, (Aldrich Chemical, Milwaukee, Wis.) was dissolvedin 5 mL of an acetic acid solution selected from the followingconcentrations, respectively: 40 mM and 80 mM. The resulting solutionwas agitated at room temperature until all of the Triton X-100 wasdissolved and was then chilled in an ice-water bath.

Meanwhile, methyltrimethoxysilane, 5 mL, and tetramethoxysilane, 10 mL,(both from Gelest Inc., Tullytown, Pa.) were mixed at room temperaturein a separate, sealed flask. An aliquot of 2 mL of the mixed silanesolution was slowly added into the chilled acetic acid mixture,whereupon the silanes dissolved into the acetic acid solution after afew minutes. The resulting transparent solution was transferred into asealed polypropylene container (9.6 mm×10 cm) and kept at 45° C.undisturbed for 2 days. The solid white rod produced was subsequentlyimmersed into 100 mL 0.1 N aqueous ammonium hydroxide solution for 3days at 60° C. The monolith material was then washed with water for 2days, solvent-exchanged to methanol for 1 day, and then dried in air for5 hours. The monolith material was then dried under vacuum at 135° C.for 3 days, resulting in a white monolith material without any cracks.

The morphologies of the formed rods were observed by a scanning electronmicroscope. It was observed that a three-dimensional interconnectednetwork was formed within the rods and that the skeleton thicknessincreased as the acetic acid concentration increased. For example, themonolith material obtained from 40 mM acetic acid solution had askeleton thickness less than 0.5 μm, while the monolith materialobtained from 80 mM acetic acid solution had a skeleton thickness around4 μm.

Pore size characterization of the monolith material prepared from 80 mMacetic acid is listed in Table 12.

TABLE 12 Acetic Acid Skeleton Concentration Thickness MPD PV(1) MPDPV(2) SSA SPV APD Product (mM) (μm) (μm) (cc/g) (Å) (cc/g) (m²/g) (cc/g)(Å) 30 80 4 4.5 2.8 161 1.23 673 1.3 79

Example 31

The following experiment was carried out in order to demonstrate therelationship between skeleton thickness and incubation time. Rods wereprepared from the same sol composition and processed under similarconditions except with different incubation times.

Pluronic P-105, 0.7 g, was dissolved in a 90 mM acetic acid solution.The resulting solution was agitated at room temperature until thePluronic P-105 was completely dissolved and then chilled in an ice-waterbath.

Meanwhile, methyltrimethoxysilane, 5 mL, and tetramethoxysilane, 10 mL,(both from Gelest Inc., Tullytown, Pa.) were mixed at room temperaturein a separate, sealed flask. An aliquot of 2 mL of the mixed silanesolution was slowly added into the chilled acetic acid mixture,whereupon the silanes dissolved into the acetic acid solution after afew minutes. The resulting transparent solution was transferred into asealed polypropylene container (9.6 mm×10 cm) and kept at 45° C.undisturbed for 45 hours. The process was repeated in the same mannerexcept the resulting transparent solution was kept undisturbed for 112hours.

The solid white rods produced were subsequently immersed into 100 mL 0.1N aqueous ammonium hydroxide solution for 3 days at 60° C. The monolithmaterials were then washed with water for 2 days, solvent-exchanged tomethanol for 1 day, and then dried in air for 5 hours. The monolithmaterials were then dried under vacuum at 135° C. for 3 days, resultingin a white monolith material without any cracks.

The morphologies of the formed rods were observed by a scanning electronmicroscope. Both rods were determined to have a three dimensionalinterconnected skeleton network, and a skeleton thickness that increasedas the incubation time increased. The material with a 112 h incubatingtime had a skeleton thickness around 5 μm, while the one with a 45 hincubating time had a skeleton thickness of 3.5 μm.

Example 32

The hybrid inorganic/organic monolith material rods prepared in Example29 and 30 were immersed in 100 mL of 0.1 Ntris(hydroxymethy)aminomethane (TRIS, Aldrich Chemical, Milwaukee, Wis.)in water. The pH of the solution was adjusted to 8.0 by addingconcentrated acetic acid. The resulting solution was then enclosed in astainless steel autoclave and heated to 155° C. for 24 hours. After theautoclave cooled to room temperature, the monolith material was rinsedwith water for 2 days, with methanol for 1 day, and then dried in airfor 4 hours. The monolith material was then dried under vacuum at 100°C. for 1 day.

Pore size characteristics of the resulting rods were determined usingmercury porosimetry and multi-point N₂ sorption BET method, and theresults are compiled in Table 13. An example of the pore size over porevolume relationship, or the mesopore size distribution, before and aftersubjection to the hydrothermal autoclave process is graphed in FIG. 2,which demonstrate that the hydrothermal process narrowed the mesoporesize distribution.

TABLE 13 Product # Before Acetic Acid Prod- Hydrothermal Concentra- SSASPV APD uct # Treatment tion (mM) Template (m²/g) (cc/g) (Å) 32a 29c 70Pluronic 284 1.51 256 32b 29d 110 P-105 176 1.19 264 32c 30 80 Triton173 1.46 322 X-100

Example 33

Three rods were prepared in a similar fashion to product 29c and wereseparately immersed in 100 mL 0.1 N tris(hydroxymethy)aminomethane(TRIS, Aldrich Chemical, Milwaukee, Wis.) water solutions. Thehydrothermal process conditions, such as pH and temperature, of thethree reactions are listed in Table 14.

Pore size characteristics of the final materials using the BET methodare compiled in Table 14. As depicted, average pore size decreases bothas the pH decreases and as the temperature decreases for thehydrothermal process.

TABLE 14 Temperature of pH of 0.1N Hydrothermal SSA SPV APD Product #TRIS Solution Process (m²/g) (cc/g) (Å) 33a 8.0 155° C. 284 1.51 256 33b8.0 130° C. 324 1.58 238 33c 7.5 130° C. 379 1.72 209

Example 34

A 1.03 g amount of the dried monolith material (product 33a of Example33) was soaked in 20 mL of toluene (J.T. Baker) and refluxed for 3.5 hunder an argon atmosphere to deoxygenate and removed adsorbed water viaazeotropic distillation. After cooling to room temperature under dryargon, 0.42 g of imidazole (Aldrich Chemical) and 0.784 g ofn-octadecyltriethoxysilane (Gelest Inc., Tullytown, Pa.) were added. Thesolution was stirred and heated to 105° C. for 20 h. The monolithmaterial, after cooling, was exhaustively washed with toluene andacetone (J.T. Baker). The washed monolith material was dried at 80° C.under vacuum for 24 h. The surface concentration (μmol/m²) ofn-octadecylsilane was determined by the difference in the monolithmaterial carbon content before and after the surface modification asmeasured by elemental analysis. The resulting monolith material had a 4%increase in carbon content that is analogous to a surface coverage of0.7 (μmol/m²) of n-octadecylsilane group.

Example 35

A solution was prepared consisting of 5 mL of Sylgard 184® Part A and0.5 mL Sylgard 184® Part B (both from Dow Corning Corp., Midland, Mich.)in 100 mL ethyl acetate (HPLC grade, J.T. Baker). Octadecyl (C₁₈)functionalized and end capped hybrid particles of product type 25u inExample 25 were then suspended in the Sylgard®/ethyl acetate solution ina ratio of 100 mg particles per 1 milliliter of solution. The mixturewas agitated manually to wet the particles, and the suspension wassonicated for 2 minutes (Branson 5510 ultrasonic bath or equivalent,Branson Ultrasonic Corp., Danbury, Conn.). The particles were thenisolated by vacuum filtration (0.5 μm Tyvek® filter paper or equivalent,DuPont, Wilmington, Del.), which was monitored and stopped when thegross liquid was removed from the filter cake. The filter cakes wereallowed to “air dry” at room temperature for 2 days and were then vacuumdried at 70° C. and <15 mm Hg.

The Sylgard 184® pre-coated particles, 4.80 g, were combined with 1.20 gof 5 μm spherical Symmetry silica particles (Waters Corporation) in a 50mL polypropylene bottle. The mixture was blended manually for 5 minutes,and the mixed particles were then slurry packed into 2.1×50 mm HPLCcolumns using a downward slurry technique. The column packing apparatuscomprised a high-pressure liquid packing pump (Model No: 10-500FS 100 orequivalent, SC Hydraulic Engineering Corp., Los Angeles, Calif.) and aslurry packing reservoir (15 mL), which was connected to the assembledcolumn. A slurry of the mixed stationary phase was prepared intetrahydrofuran-isopropanol 70:30 (v/v) mixture, sonicated for 5 min andpoured into the packing reservoir. The reservoir was then closed andmethanol was pumped through the column to a pressure of 9000-9500 PSI.After sufficient time for bed consolidation the pump was turned off, andthe pressure was released.

The packed columns were purged with methanol and then ethyl acetate at0.4 mL/min flow rate using a high pressure chromatography pump (Waters590 HPLC pump or equivalent), whereupon greater than 10 mL of each purgesolvent was collected. A Sylgard 184® solution was prepared bydissolving 15 mL Sylgard 184® Part A and 1.5 mL Sylgard 184® Part B in100 mL ethyl acetate. The solutions were used either within 2 hours ofpreparation or after allowing pre-polymerization (aging) for 3, 25 and72 hours, respectively. The Sylgard 184® solutions were pumped throughpacked columns (see above) separately at 0.2 mL/min flow rate using aWaters 590 HPLC pump until 3 mL of effluent was collected. The columnpressure was allowed to drop for 30 minutes prior to disconnection. Thecolumns were left uncapped in a chemical fume hood's air stream for 18h, transferred to a 65° C. convection oven for 28 h, and then cooled toroom temperature. The coalesced particle hybrid monoliths were thenextruded from the columns and vacuum dried for 7.5 h at roomtemperature.

The specific surface area (SSA), specific pore volumes (SPV) and theaverage pore diameters (APD) of the resultant materials are listed inTable 15 and were measured using the multi-point N₂ sorption method(Micromeritics ASAP 2400 instrument or equivalent, Micromeritics,Norcross, Ga.). The specific surface area was calculated using the BETmethod, the specific pore volume was the single point value determinedat P/P₀>0.98, and the average pore diameter was calculated from thedesorption leg of the isotherm using the BJH method.

TABLE 15 Pre- Coalesced polymerization particles Prod- Sylgard ® time ofSylgard observed SSA SPV APD uct treatment 184 ® solution by SEM? (m²/g)(cm³/g) (Å) 35a Yes <2 hours No 113 0.42 114 35b Yes  3 hours Yes 1190.45 115 35c Yes 25 hours Yes 120 0.45 114 35d Yes 72 hours Partial 1180.44 116 Con- None NA NA 129 0.48 117 trol

Example 36

A non-ionic surfactant, Pluronic P-105 (P-105; BASF, Mount Olive, N.J.)or Triton X-100 (X-100; Aldrich Chemical) was dissolved in a glacialacetic acid (J.T. Baker) and water solution. To this solution, a mixtureof methyltrimethoxysilane and tetramethoxysilane (both from Gelest Inc.)was added at 0° C. with stirring for 30 min

The resulting solution was sealed in a glass vial and kept at 45° C. for3 days. The solution solidified, and a white solid rod was produced.Thus rod was then immersed into an 1 M ammonium hydroxide (J.T. Baker)water solution at 60° C. for 3 days. After washing out the ammoniumhydroxide using water, the rod was immersed in a tris(hydroxymethyl)aminomethane (TRIS; Aldrich Chemical) and water solution. The pH of thesolution was then adjusted as desired by adding glacial acetic acid(J.T. Baker). The resulting solution and immersed rod was then enclosedin a stainless steel autoclave and heated to 155° C. for 24 h.

After the autoclave cooled down to room temperature, the rod was washedrepeatedly with water and methanol, dried in the air for 4 h, and thenvacuum dried at 80C. for 1 day. Detailed reagent amounts and reactionconditions used to prepare these hybrid monolith materials are listed inTable 16. The post hydrothermal compositions were confirmed usingcombustion analysis or % CHN (CE-440 Elemental Analyzer or equivalent;Exeter Analytical Inc., North Chelmsford, Mass.), ¹³C and ²⁹Si CPMAS NMRspectroscopy (Bruker MSL-300 NMR spectrometer or equivalent, Bruker,Billerica, Mass.).

The median macropore diameter (MPD) and macropore pore volume (MPV) ofthe resultant materials was measured by Mercury Porosimetry(Micromeritics AutoPore II 9220 or AutoPore IV or equivalent,Micromeritics, Norcross, Ga.) and are listed in Table 17. The specificsurface area (SSA), specific pore volumes (SPV), and average porediameters (APD) of the resultant materials are listed in Table 17 andwere measured and calculated as described in Example 35. The microporesurface area (MPA), which is defined as the surface area in pores withdiameters less than or equal to 34 Å, was also determined from theadsorption leg of the isotherm using the BJH method.

Example 37

A non-ionic surfactant, Pluronic P-105 (P-105; BASF) or Pluronic P-123(P-123; BASF) was dissolved in a glacial acetic acid (J.T. Baker) watersolution. To this solution, a mixture of 1,2-bis-(trimethoxysilyl)ethane(Aldrich Chemical) and tetramethoxysilane (Gelest Inc.) was added at 0°C. with stirring for 30 min. The resulting solution was sealed in aglass vial and kept at 45° C. for 2 days. The solution solidified, and awhite solid rod was produced, which was then immersed into an 1 Mammonium hydroxide (J.T. Baker) water solution at 60° C. for 2 days.After washing out the ammonium hydroxide using water, the rod wasimmersed in a tris(hydroxymethyl)aminomethane (TRIS, Aldrich Chemical)and water solution. The pH of the solution was then adjusted as desiredby adding glacial acetic acid (J.T. Baker). The resulting solution andimmersed rod was then enclosed in a stainless steel autoclave and heatedto 155° C. for 24 h.

After the autoclave cooled down to room temperature, the rod was washedrepeatedly with water and methanol, dried in the air for 4 h, and thenvacuum dried at 80° C. for 1 day. Detailed reagent amounts and reactionconditions to prepare these hybrid monolith materials are listed inTable 16. The post hydrothermal compositions were confirmed using % CHN,¹³C and ²⁹Si CPMAS NMR spectroscopy as described in Example 36.

The median macropore diameter (MPD) and macropore pore volume (MPV) ofthese resultant materials are listed in Table 17 and were measured asdescribed in Example 36. The specific surface area (SSA), specific porevolume (SPV), average pore diameter (APD), and micropore surface area(MPA) of these resultant materials are listed in Table 13 were measuredand calculated as described in Examples 35 and 36.

Example 38

A non-ionic surfactant, Triton 405 (405; Aldrich Chemical) or TritonX-100 (X-100; Aldrich Chemical) was dissolved in a glacial acetic acid(J.T. Baker) water solution. To this solution, a mixture ofmethacryloxypropyltrimethoxysilane and tetramethoxysilane (both fromGelest Inc.) was added at 0° C. with stirring for 30 min. The resultingsolution was sealed in a glass vial and kept at 45° C. for 3 days. Thesolution solidified, and white solid rod was produced, which was thenimmersed into an 1 M ammonium hydroxide (J.T. Baker) water solution at60° C. for 3 days. After washing out the ammonium hydroxide using water,the rod was immersed in a tris(hydroxymethyl)aminomethane (TRIS, AldrichChemical) and water solution. The pH of the solution was then adjustedas desired by adding glacial acetic acid (J.T. Baker). The resultingsolution and immersed rod was then enclosed in a stainless steelautoclave and heated to 155° C. for 24 h.

After the autoclave cooled down to room temperature, the rod was washedrepeatedly with water and methanol, dried in the air for 4 h, and thenvacuum dried at 80° C. for 1 day. Detailed reagent amounts and reactionconditions to prepare these hybrid monolith materials are listed inTable 16.

The methacryloxypropyl group of the hybrid materials were converted intoa 3-hydroxypropyl group via hydrolysis of the ester bond duringhydrothermal treatment in the autoclave. The post hydrothermal treatmentcomposition of the hybrid material's organic substituent is thusdescribed as a 3-hydroxypropyl or propanol [HO(CH₂)₃SiO_(1.5)] group.Conversion of the ester into the alcohol group was observed by adecrease in the % C of the rods before vs. after treatment. The posthydrothermal compositions were confirmed using % C, ¹³C and ²⁹Si CPMASNMR spectroscopy as described in Example 36.

The median macropore diameter (MPD) and macropore pore volume (MPV) ofthese resultant materials are listed in Table 13 and were measured asdescribed in Example 36. The specific surface area (SSA), specific porevolume (SPV), average pore diameter (APD), and micropore surface area(MPA) of these resultant materials are listed in Table 17 and weremeasured as described in Examples 35 and 36.

TABLE 16 Post-Hydrothermal Hydrothermal TRIS Conditions Composition ofHybrid Surfactant Surfactant Acetic Acid Water TMOS RTMOS Amount Conc.Temp. Product Material Type (g) (mg) (mL) (mL) (mL) (mL/g) (Molarity) pH(° C.) 36a SiO₂/(CH₃SiO_(1.5))_(0.5) P-105 2.8 84 20 5.33 2.67 210 0.18.0 155 36b SiO₂/(CH₃SiO_(1.5))_(0.5) P-105 0.7 27 5 1.33 0.67 160 0.18.9 155 36c SiO₂/(CH₃SiO_(1.5))_(0.5) P-105 0.7 33 5 1.33 0.67 500 0.18.0 155 36d SiO₂/(CH₃SiO_(1.5))_(0.5) X-100 0.7 24 5 1.33 0.67 350 0.18.0 155 37a SiO₂/(SiO_(1.5)CH₂CH₂SiO_(1.5))_(0.15) P-105 0.8 27 5 1.60.4 70 0.1 8.0 155 37b SiO₂/(SiO_(1.5)CH₂CH₂SiO_(1.5))_(0.15) P-105 0.927 5 1.6 0.4 70 0.1 8.0 155 37c SiO₂/(SiO_(1.5)CH₂CH₂SiO_(1.5))_(0.15)P-105 0.7 27 5 1.6 0.4 200 0.3 9.0 155 37dSiO₂/(SiO_(1.5)CH₂CH₂SiO_(1.5))_(0.25) P-123 0.7 30 5 1.43 0.57 100 0.310.6 155 37e SiO₂/(SiO_(1.5)CH₂CH₂SiO_(1.5))_(0.25) P-123 0.6 30 5 1.430.57 200 0.1 10.6 155 37f SiO₂/(SiO_(1.5)CH₂CH₂SiO_(1.5))_(0.25) P-1230.65 30 5 1.43 0.57 200 0.1 10.6 155 37gSiO₂/(SiO_(1.5)CH₂CH₂SiO_(1.5))_(0.25) P-123 14.1 600 100 28.6 11.4 200.1 10.5 155 38a SiO₂/[HO(CH₂)₃SiO_(1.5)]_(0.15) X-100 0.7 4.2 5 1.6 0.4670 1.2 10.6 155 38b SiO₂/[HO(CH₂)₃SiO_(1.5)]_(0.15) 405 0.7 4.2 5 1.60.4 670 1.2 10.6 155 38c SiO₂/[HO(CH₂)₃SiO_(1.5)]_(0.15) X-100 1.31 4.25 1.6 0.4 80 0.1 8.0 155

TABLE 17 MPD MPV SSA SPV APD MPA Product (μm) (cc/g) (m²/g) (cc/g) (Å)(m²/g) 36a 2.4 3.56 284 1.51 256 126 36b 6.2 2.75 171 1.22 179 42 36c17.6 0.85 177 1.19 264 50 36d 5.4 2.8 173 1.46 322 47 37a 2.98 3.11 1861.47 203 7 37b 0.76 2.91 220 1.89 237 21 37c 4.7 1.38 214 1.91 290 5937d 4.4 2.42 171 1.29 219 9 37e 1.34 2.1 130 1.04 240 14 37f 1.21 2.11141 1.12 246 14 37g 2.14 3.7 208 1.4 197 7 38a 5.1 3.15 162 0.96 234 3738b 28.2 3.15 151 0.81 214 39 38c 1.5 2.77 260 0.71 77 20

Example 39

Hybrid monoliths prepared according to Examples 36, 37, and 38 wereimmersed in a 1 M hydrochloric acid solution (Aldrich Chemical) for 24 hat 98° C. After acid treatment was complete, the monoliths were washedwith water to a pH above 5 followed by acetone washing (J.T. Baker). Themonoliths were then dried at 80° C. under vacuum for 24 h.

Example 40

Hybrid monoliths prepared according to example 36a and 37a were acidwashed according to Example 39. The hybrid monoliths were then immersedinto 2100 mL toluene and heated to reflux for 2 h to remove residualwater by azeotropic distillation. Under a blanket of argon protection,the reaction was cooled to room temperature, and 16.3 g ofoctadecyltrichlorosilane (Aldrich Chemical) and 3.43 g of imidazole(from ACROS, Pittsburgh, Pa.) were slowly added to the reaction mixture.The reaction was then heated to 110° C. for 24 h.

The monoliths were subsequently washed twice with fresh toluene at 110°C. for 30 min, and washed twice with acetone at room temperature, for 30min Without drying, the monoliths were immersed into 2100 mL of 0.12 Mammonium acetate solution and heated to 60° C. for 2 h. The monolithswere then washed by water and acetone and dried under vacuum at 80° C.for 24 h. The surface concentration (μmol/m²) of n-octadecylsilane wasdetermined by the difference in the monolith material % C content beforeand after the surface modification as measured by % C (CE-440 ElementalAnalyzer or equivalent; Exeter Analytical Inc., North Chelmsford, Mass.)

A second step surface modification (or end capping) of the previouslymodified monoliths was performed with chlorotrimethylsilane (AldrichChemical). Accordingly, ODS modified monoliths were immersed into 2 Ltoluene and heated to reflux for 2 h to remove any residue water byazeotropic distillation. Under a blanket of argon protection, thereaction was cooled down to room temperature, and 4.56 g ofchlorotrimethylsilane and 3.43 g of imidazole (from ACROS) were slowlyadded to the reaction mixture. The reaction was then heated to 110° C.for 4 h.

The monoliths were subsequently washed twice with fresh toluene at 110°C. for 30 min, washed twice with acetone at room temperature, for 30min, and dried under vacuum at 80° C. for 24 h. The carbon content wasmeasured by combustion analysis as described in Example 36. Table 18lists the monolith materials used in the reaction, the surfaceconcentration of the resultant bonded octadecylsilane (ODS) group, andthe total % C of the final monolith after end capping.

TABLE 18 Hybrid Material Hybrid ODS Surface % C Final Prior to ODSMaterial Concentration Modified Product Modification (g) (μmol/m²)Monolith 40a 36a 12.5 2.84 21.97 40b 37a 16.0 1.92 18.16

Example 41

Hybrid monoliths prepared according to example 38a were acid washedaccording to Example 39. The hybrid monoliths (1 g) were then immersedinto 30 mL toluene and heated to reflux for 2 h to remove any residualwater by azeotropic distillation. Under a blanket of argon protection,the reaction was cooled down to room temperature, and 0.61 g ofdodecylisocyanate (Aldrich Chemical) was slowly added. The reaction wasthen heated to 110° C. for 24 h.

The monoliths were subsequently washed with fresh toluene and acetonetwice each at room temperature, for 30 min Without drying, the monolithswere immersed into 100 mL 1% trifluoroacetic acid acetone/water solution(v/v 1/1) and heated to 60° C. for 30 min. The monoliths were thenwashed by water and acetone, and dried under vacuum at 80° C. for 24 h.The reaction of the dodecyl isocyanate molecule with the hybridmonolith's hydroxyl group to form a carbamate group and thereby connectthe dodecyl chain to the monolith's skeletal structure through acovalent organic bond was established by a 10.84% C difference in themonolith material carbon content before and after the surfacemodification. The % C was measured by combustion analysis as describedin Example 36. That increase in % C is analogous to a surfaceconcentration of 2.76 μmol/m² of O-propylsilyl N-dodecyl carbamategroups. Furthermore, ¹³C CPMAS NMR spectroscopy of the particles showedresonances consistent with addition product, where 40% of the propanolgroups were converted to carbamate groups, and the remaining propanolgroups remained unreacted.

Example 42

Hybrid monoliths prepared according to example 38a were acid washedaccording to Example 39. In a three-neck flask, 1 g of the hybridmonoliths were immersed into a mixture of 50 mL tetrahydrofuran, 0.72 g1,2-epoxydodecane, and 0.06 g iron(III) chloride (all from AldrichChemical) at room temperature. The mixture was kept at room temperaturewith stiffing for 4 h. The hybrid monolith was then removed from thereaction mixture and extensively washed with 1% (by w %) hydrochloricacid water solution, acetone/water, and acetone. The monoliths were thendried under vacuum at 80° C. for 24 h.

Reaction of the 1,2-epoxydodecane molecule with the hybrid monolith'shydroxyl group to form a hydroxyl substituted ether group and therebyconnect the decyl chain to the monolith's skeletal structure through acovalent organic bond was established by a 6.55% C difference in themonolith material carbon content before and after the surfacemodification. The % C was measured by combustion analysis as describedin Example 30. That increase in % C is analogous to a surfaceconcentration of 1.80 μmol/m² of decyl ether groups. Furthermore, ¹³CCPMAS NMR spectroscopy of the particles showed resonances consistentwith addition product, where 30% of the propanol groups were convertedto ether groups, and the remaining propanol groups remained unreacted.

Example 43

Hybrid monoliths prepared according to example 38a were acid washedaccording to Example 39. A 1 g quantity of the hybrid monoliths was thenimmersed into 1000 mL toluene with 0.37 g p-toluenesulfonic acidmonohydrate (Aldrich Chemical) and heated to reflux for 2 h to removeany residual water by azeotropic distillation. Under a blanket of argonprotection, an additional funnel filled with a mixture of 15 mL tolueneand 3.07 g of n-decylalcohol (Aldrich Chemical) was attached directlyonto the top of the flask, and the solution was slowly added to thereaction mixture over a period of 2 h. The reaction was then heated toreflux for 24 h, whereupon the water generated as one of the reactionproducts was continually removed by azeotropic distillation. After thereaction was cooled down, the monoliths were then washed by water andacetone, and dried under vacuum at 80° C. for 24 h.

The reaction of the n-decylalcohol molecule with the hybrid monolith'shydroxyl group to form an ether group and thereby connect the decylchain to the monolith's skeletal structure through a covalent organicbond was established by a 6.04% C difference in the monolith materialcarbon content before and after the surface modification. The % C wasmeasured by combustion analysis as described in Example 36. Thatincrease in % C is analogous to a surface concentration of 1.66 μmol/m²of decyl ether groups. Furthermore, ¹³C CPMAS NMR spectroscopy of theparticles showed resonances consistent with addition product, where 30%of the propanol groups were converted to ether groups, and the remainingpropanol groups remained unreacted.

INCORPORATION BY REFERENCE

The entire contents of all patents, published patent applications andother references cited herein are hereby expressly incorporated hereinin their entireties by reference.

EQUIVALENTS

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, numerous equivalents to thespecific procedures described herein. Such equivalents were consideredto be within the scope of this invention and are covered by thefollowing claims. The contents of all references, issued patents, andpublished patent applications cited throughout this application arehereby incorporated by reference.

What is claimed is:
 1. A method of preparation of a porousinorganic/organic hybrid monolith material, comprising coalesced porousparticles of hybrid silica having a chromatography-enhancing poregeometry, comprising the steps of a) prepolymerizing a mixture of one ormore organoalkoxysilanes and a tetraalkoxysilane in the presence of anacid catalyst to produce a polyorganoalkoxysiloxane; b) preparing anaqueous suspension of said polyorganoalkoxysiloxane, said suspensionfurther comprising a surfactant or combination of surfactants, andgelling in the presence of a base catalyst so as to produce poroushybrid particles; c) modifying the pore structure of said porous hybridparticles by hydrothermal treatment; and d) coalescing said poroushybrid particles to form a monolith material thereby preparing a porousinorganic/organic hybrid monolith material.
 2. A porousinorganic/organic hybrid monolith material comprising coalesced poroushybrid particles of hybrid silica having a chromatographically-enhancingpore geometry, produced by the process of a) prepolymerizing a mixtureof one or more organoalkoxysilanes and a tetraalkoxysilane in thepresence of an acid catalyst to produce a polyorganoalkoxysiloxane; b)preparing an aqueous suspension of said polyorganoallcoxysiloxane, saidsuspension further comprising a surfactant or a combination ofsurfactants, and gelling in the presence of a base catalyst so as toproduce porous hybrid particles; c) modifying the pore structure of saidporous hybrid particles by hydrothermal treatment; and coalescing saidporous hybrid particles to form a monolith material.
 3. A porousinorganic/organic hybrid monolith material, comprising coalesced porousinorganic/organic hybrid particles having achromatographically-enhancing pore geometry and a formulaSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) wherein said hybrid particles have beensurface modified with octadecyltrichlorosilane and wherein any freesilanol groups remaining from said surface modification are endcappedwith chlorotrimethylsilane.
 4. A porous inorganic/organic hybridmonolith material comprising coalesced porous hybrid particles of hybridsilica having a chromatographically-enhancing pore geometry and aformula SiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) produced by the process of a)prepolymerizing a 0.25/1.0 mole ratio mixture ofbis(triethoxysilyl)ethane and tetraethoxysilane in the presence of 0.1molar hydrochloric acid to produce a polyorganosiloxane; b) preparing anaqueous suspension of said polyorganoalkoxysiloxane, said suspensionfurther comprising the surfactant Triton X-100, and gelling saidsuspension in the presence of a ammonium hydroxide so as to produceporous hybrid particles; c) modifying the pore structure of said poroushybrid particles by hydrothermal treatment at 155° C. for 20 h in 0.3 Mtris(hydroxymethyl)aminomethane, pH adjusted to 9.80; d) sizing to anominal 2 μm particle diameter; acid washing in a 1 molar hydrochloricacid solution; e) further surface modifying withoctadecyltrichlorosilane wherein any free silanol groups remaining fromsaid surface modification are endcapped with chlorotrimethylsilane; andg) coalescing said porous hybrid particles to form a monolith material.5. A porous inorganic/organic hybrid monolith material having achromatographically-enhancing pore geometry and a formulaSiO₂/[CH₃SiO_(1.5)]_(0.5) wherein said hybrid material has been surfacemodified with octadecyltrichlorosilane and wherein any free silanolgroups remaining from said surface modification procedure are endcappedwith chlorotrimethylsilane and wherein said material contains aplurality of macropores sufficient to result in reduced backpressure atchromatographically-useful flow rates.
 6. A porous inorganic/organichybrid monolith material having a chromatographically-enhancing poregeometry and a formula SiO₂/[CH₃SiO_(1.5)]_(0.5), produced by theprocess of a) preparing an aqueous solution of methyltrimethoxysilaneand a tetramethoxysilane in the presence of a 0.07 molar acetic acidsolution and the surfactant Pluronic P-105 or Trition X-100 to produce apolyorganoalkoxysiloxane; a) incubating said solution for 3 days at 45°C., resulting in a three-dimensional gel having a continuous,interconnected pore structure; b) aging the gel in 1 molar ammoniumhydroxide at 60° C. for 3 days to yield a solid monolith material; c)rinsing the monolith material with water; d) modifying the porestructure of said monolith material by hydrothermal treatment at 155° C.for 20 h in 0.1 molar tris(hydroxymethyl)aminomethane, p1-1 adjusted to8.0; e) rinsing the monolith material with water followed by a solventexchange; g) 1) acid washing the monolith material in 1 molarhydrochloric acid for 24 hours at 98° C.; rinsing the monolith materialwith water followed by a solvent exchange; h) drying the monolithmaterial at room temperature drying and at 80° C. under vacuum; and i)further surface modifying with octadecyltrichlorosilane wherein any freesilanol groups remaining from said surface modification are endcappedwith chlorotrimethylsilane.
 7. A porous inorganic/organic hybridmonolith material having a chromatographically-enhancing pore geometryand a formula SiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25) wherein said hybridmaterial has been surface modified with octadecyltrichlorosilane andwherein any free silanol groups remaining from said surface modificationprocedure are endcapped with chlorotrimethylsilane and wherein saidmaterial contains a plurality of macropores sufficient to result inreduced backpressure at chromatographically-useful flow rates.
 8. Aporous inorganic/organic hybrid monolith material havingachromatographically-enhancing pore geometry and a formulaSiO₂/[C₂H₄(SiO_(1.5))₂]_(0.25), produced by the process of a) preparingan aqueous solution 1,2-bis(trimethoxysilyl)ethane andtetramethoxysilane in the presence of a 0.09 molar acetic acid solutionand the surfactant Pluronic P-123 to produce a polyorganoalkoxysiloxane;b) incubating said solution for 2 days at 45° C., resulting in athree-dimensional gel having a continuous, interconnected porestructure; c) aging the gel in 1 molar ammonium hydroxide at 60° C. for2 days to yield a solid monolith material; d) rinsing the monolithmaterial with water; modifying the pore structure of said monolithmaterial by hydrothermal treatment at 155° C. for 24 h in 0.1 Mtris(hydroxymethyl)aminomethane, pH adjusted to 10.6; f) rinsing themonolith material with water followed by a solvent exchange; g) acidwashing the monolith material in 1 molar hydrochloric acid for 24 hoursat 98° C.; h) rinsing the monolith material with water followed by asolvent exchange; i) drying the monolith material at room temperaturedrying and at 80° C. under vacuum, and j) further surface modifying withoctadecyltrichlorosilane wherein any free silanol groups remaining fromsaid surface modification are endcapped with chlorotrimethylsilane.
 9. Aporous inorganic/organic hybrid monolith material having achromatographically-enhancing pore geometry and a formulaSiO₂/[HOC₃H₆SiO_(1.5)]_(0.15) wherein said hybrid material has beensurface modified with dodecylsiocyante and wherein said materialcontains a plurality of macropores sufficient to result in reducedbackpressure at chromatographically-useful flow rates.
 10. A porousinorganic/organic hybrid monolith material having a 30chromatographically-enhancing pore geometry and a formulaSiO₂/[HOC₃H₆SiO_(1.5)]_(0.15), produced by the process of a) preparingan aqueous solution methacryloxypropyltrimethoxysilane andtetramethoxysilane in the presence of a 0.015 molar acetic acid solutionand the surfactant Triton X-100 or Triton 405 to produce apolyorganoalkoxysiloxane; b) incubating said solution for 3 days at 45°C., resulting in a three-dimensional gel having a continuous,interconnected pore structure; c) aging the gel in 1 molar ammoniumhydroxide at 60° C. for 3 days to yield a solid monolith material; d)rinsing the monolith material with water; e) modifying the porestructure of said monolith material by hydrothermal treatment at 155° C.for 24 h in 0.1 M tris(hydroxymethyl)aminomethane, pH adjusted to 10.6;f) rinsing the monolith material with water followed by a solventexchange; g) acid washing the monolith material in 1 molar hydrochloricacid for 24 hours at 98° C.; h) rinsing the monolith material with waterfollowed by a solvent exchange; i) drying the monolith material at roomtemperature drying and at 80° C. under vacuum, and j) further surfacemodifying with dodecylisocyanate.